TGF-β Pathway in Salivary Gland Fibrosis
Abstract
:1. Introduction
2. Overview of the TGF-β Signaling Pathway
2.1. TGF-β Family Members and Downstream Signaling
2.2. TGF-β Latency and Activation
3. TGF-β Signaling in Fibrosis
4. TGF-β Signaling in Salivary Gland Fibrosis
4.1. Sialadenitis
4.2. Post-Radiation Induced Salivary Gland Fibrosis
4.3. Sjögren’s Syndrome
5. Potential Therapeutic Strategies for Fibrosis
5.1. Inhibition of Pro-Fibrotic Ligand and Receptor Activity
5.2. Activation of Anti-Fibrotic Ligand and Receptor
5.3. Inhibition of the SMAD Pathway
5.4. Issues in Clinical Delivery of BMP
6. Conclusions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
TGF-β | Transforming growth factor beta |
BMP | Bone morphogenetic protein |
ECM | Extracellular matrix |
TGFβR | Transforming growth factor beta receptor |
ALK | Activin receptor-like kinase |
(R)-SMAD | Regulated-SMAD |
(Co)-SMAD | Common partner-SMAD |
(I)-SMAD | Inhibitory-SMAD |
LAP | Latency-associated protein |
SLC | Small latent complex |
LTBP | Latent TGF-β binding protein |
LLC | Large latent complex |
EMT | Epithelial–mesenchymal transition |
EndMT | Endothelial-mesenchymal transition |
MMP | Matrix metallopeptidase |
SS | Sjögren’s syndrome |
IL | Interleukin |
Th17 | T helper 17 |
References
- Hayashi, H.; Sakai, T. Biological significance of local tgf-β activation in liver diseases. Front. Physiol. 2012, 3, 12. [Google Scholar] [CrossRef] [Green Version]
- Kingsley, D.M. The tgf-beta superfamily: New members, new receptors, and new genetic tests of function in different organisms. Genes Dev. 1994, 8, 133–146. [Google Scholar] [CrossRef] [Green Version]
- Horiguchi, M.; Ota, M.; Rifkin, D.B. Matrix control of transforming growth factor-β function. J. Biochem. 2012, 152, 321–329. [Google Scholar] [CrossRef] [Green Version]
- Xu, J.; Lamouille, S.; Derynck, R. Tgf-beta-induced epithelial to mesenchymal transition. Cell Res. 2009, 19, 156–172. [Google Scholar] [CrossRef] [PubMed]
- Morikawa, M.; Derynck, R.; Miyazono, K. Tgf-β and the tgf-β family: Context-dependent roles in cell and tissue physiology. Cold Spring Harb. Perspect. Biol. 2016, 8, a021873. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zinski, J.; Tajer, B.; Mullins, M.C. Tgf-β family signaling in early vertebrate development. Cold Spring Harb. Perspect. Biol. 2018, 10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- David, C.J.; Massague, J. Contextual determinants of tgf beta action in development, immunity and cancer. Nat. Rev. Mol. Cell Biol. 2018, 19, 419–435. [Google Scholar] [CrossRef]
- Batlle, E.; Massagué, J. Transforming growth factor-β signaling in immunity and cancer. Immunity 2019, 50, 924–940. [Google Scholar] [CrossRef]
- Chen, W.J.; ten Dijke, P. Immunoregulation by members of the tgf beta superfamily. Nat. Rev. Immunol. 2016, 16, 723–740. [Google Scholar] [CrossRef]
- Pedersen, A.M.L.; Sørensen, C.E.; Proctor, G.B.; Carpenter, G.H.; Ekström, J. Salivary secretion in health and disease. J. Oral Rehabil. 2018, 45, 730–746. [Google Scholar] [CrossRef]
- Lasisi, T.J.; Shittu, S.T.; Oguntokun, M.M.; Tiamiyu, N.A. Aging affects morphology but not stimulated secretion of saliva in rats. Ann. Ib. Postgrad. Med. 2014, 12, 109–114. [Google Scholar] [PubMed]
- Roberts, A.B.; Kim, S.J.; Noma, T.; Glick, A.B.; Lafyatis, R.; Lechleider, R.; Jakowlew, S.B.; Geiser, A.; O’Reilly, M.A.; Danielpour, D.; et al. Multiple forms of tgf-beta: Distinct promoters and differential expression. Ciba Found. Symp. 1991, 157, 7–15; discussion 15–28. [Google Scholar] [PubMed]
- Hinck, A.P.; Mueller, T.D.; Springer, T.A. Structural biology and evolution of the tgf-β family. Cold Spring Harb. Perspect. Biol. 2016, 8, a022103. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Felin, J.E.; Mayo, J.L.; Loos, T.J.; Jensen, J.D.; Sperry, D.K.; Gaufin, S.L.; Meinhart, C.A.; Moss, J.B.; Bridgewater, L.C. Nuclear variants of bone morphogenetic proteins. BMC Cell Biol. 2010, 11, 20. [Google Scholar] [CrossRef] [Green Version]
- Shi, M.; Zhu, J.; Wang, R.; Chen, X.; Mi, L.; Walz, T.; Springer, T.A. Latent tgf-β structure and activation. Nature 2011, 474, 343–349. [Google Scholar] [CrossRef] [Green Version]
- Mi, L.Z.; Brown, C.T.; Gao, Y.; Tian, Y.; Le, V.Q.; Walz, T.; Springer, T.A. Structure of bone morphogenetic protein 9 procomplex. Proc. Natl. Acad. Sci. USA 2015, 112, 3710–3715. [Google Scholar] [CrossRef] [Green Version]
- Hata, A.; Chen, Y.G. Tgf-beta signaling from receptors to smads. Cold Spring Harb. Perspect. Biol. 2016, 8, a022061. [Google Scholar] [CrossRef]
- Heldin, C.H.; Moustakas, A. Signaling receptors for tgf-β family members. Cold Spring Harb. Perspect. Biol. 2016, 8, a022053. [Google Scholar] [CrossRef] [Green Version]
- Lawler, S.; Feng, X.H.; Chen, R.H.; Maruoka, E.M.; Turck, C.W.; Griswold-Prenner, I.; Derynck, R. The type ii transforming growth factor-beta receptor autophosphorylates not only on serine and threonine but also on tyrosine residues. J. Biol. Chem. 1997, 272, 14850–14859. [Google Scholar] [CrossRef] [Green Version]
- De Crescenzo, G.; Pham, P.L.; Durocher, Y.; O’Connor-McCourt, M.D. Transforming growth factor-beta (tgf-beta) binding to the extracellular domain of the type ii tgf-beta receptor: Receptor capture on a biosensor surface using a new coiled-coil capture system demonstrates that avidity contributes significantly to high affinity binding. J. Mol. Biol. 2003, 328, 1173–1183. [Google Scholar]
- Cheifetz, S.; Bassols, A.; Stanley, K.; Ohta, M.; Greenberger, J.; Massagué, J. Heterodimeric transforming growth factor beta. Biological properties and interaction with three types of cell surface receptors. J. Biol. Chem. 1988, 263, 10783–10789. [Google Scholar] [PubMed]
- Derynck, R.; Budi, E.H. Specificity, versatility, and control of tgf-β family signaling. Sci. Signal. 2019, 12, eaav5183. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bilandzic, M.; Stenvers, K.L. Betaglycan: A multifunctional accessory. Mol. Cell Endocrinol. 2011, 339, 180–189. [Google Scholar] [CrossRef] [PubMed]
- Lo, R.S.; Chen, Y.G.; Shi, Y.; Pavletich, N.P.; Massagué, J. The l3 loop: A structural motif determining specific interactions between smad proteins and tgf-beta receptors. EMBO J 1998, 17, 996–1005. [Google Scholar] [CrossRef] [Green Version]
- Goto, K.; Kamiya, Y.; Imamura, T.; Miyazono, K.; Miyazawa, K. Selective inhibitory effects of smad6 on bone morphogenetic protein type i receptors. J. Biol. Chem. 2007, 282, 20603–20611. [Google Scholar] [CrossRef] [Green Version]
- Hata, A.; Lagna, G.; Massagué, J.; Hemmati-Brivanlou, A. Smad6 inhibits bmp/smad1 signaling by specifically competing with the smad4 tumor suppressor. Genes Dev. 1998, 12, 186–197. [Google Scholar] [CrossRef] [Green Version]
- Imamura, T.; Takase, M.; Nishihara, A.; Oeda, E.; Hanai, J.; Kawabata, M.; Miyazono, K. Smad6 inhibits signalling by the tgf-beta superfamily. Nature 1997, 389, 622–626. [Google Scholar] [CrossRef]
- Hayashi, H.; Abdollah, S.; Qiu, Y.; Cai, J.; Xu, Y.Y.; Grinnell, B.W.; Richardson, M.A.; Topper, J.N.; Gimbrone, M.A., Jr.; Wrana, J.L.; et al. The mad-related protein smad7 associates with the tgfbeta receptor and functions as an antagonist of tgfbeta signaling. Cell 1997, 89, 1165–1173. [Google Scholar] [CrossRef] [Green Version]
- Souchelnytskyi, S.; Nakayama, T.; Nakao, A.; Morén, A.; Heldin, C.H.; Christian, J.L.; ten Dijke, P. Physical and functional interaction of murine and xenopus smad7 with bone morphogenetic protein receptors and transforming growth factor-beta receptors. J. Biol. Chem. 1998, 273, 25364–25370. [Google Scholar] [CrossRef] [Green Version]
- Nakao, A.; Afrakhte, M.; Morén, A.; Nakayama, T.; Christian, J.L.; Heuchel, R.; Itoh, S.; Kawabata, M.; Heldin, N.E.; Heldin, C.H.; et al. Identification of smad7, a tgfbeta-inducible antagonist of tgf-beta signalling. Nature 1997, 389, 631–635. [Google Scholar] [CrossRef]
- Zhang, Y.E. Non-smad signaling pathways of the tgf-beta family. Cold Spring Harb. Perspect. Biol. 2017, 9, a022129. [Google Scholar] [CrossRef] [PubMed]
- Yue, J.; Mulder, K.M. Activation of the mitogen-activated protein kinase pathway by transforming growth factor-beta. Methods Mol. Biol. 2000, 142, 125–131. [Google Scholar] [PubMed]
- Kim, H.-J.; Kim, J.-G.; Moon, M.-Y.; Park, S.-H.; Park, J.-B. Iκb kinase γ/nuclear factor-κb-essential modulator (ikkγ/nemo) facilitates rhoa gtpase activation, which, in turn, activates rho-associated kinase (rock) to phosphorylate ikkβ in response to transforming growth factor (tgf)-β1. J. Biol. Chem. 2014, 289, 1429–1440. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Moon, M.Y.; Kim, H.J.; Kim, J.G.; Lee, J.Y.; Kim, J.; Kim, S.C.; Choi, I.G.; Kim, P.H.; Park, J.B. Small gtpase rap1 regulates cell migration through regulation of small gtpase rhoa activity in response to transforming growth factor-β1. J. Cell Physiol. 2013, 228, 2119–2126. [Google Scholar] [CrossRef]
- Gingery, A.; Bradley, E.W.; Pederson, L.; Ruan, M.; Horwood, N.J.; Oursler, M.J. Tgf-beta coordinately activates tak1/mek/akt/nfkb and smad pathways to promote osteoclast survival. Exp. Cell Res. 2008, 314, 2725–2738. [Google Scholar] [CrossRef] [Green Version]
- Moustakas, A.; Heldin, C.-H. Non-smad tgf-β signals. J. Cell Sci. 2005, 118, 3573–3584. [Google Scholar] [CrossRef]
- Dubois, C.M.; Blanchette, F.; Laprise, M.H.; Leduc, R.; Grondin, F.; Seidah, N.G. Evidence that furin is an authentic transforming growth factor-beta1-converting enzyme. Am. J. Pathol. 2001, 158, 305–316. [Google Scholar] [CrossRef]
- Kusakabe, M.; Cheong, P.-L.; Nikfar, R.; McLennan, I.S.; Koishi, K. The structure of the tgf-β latency associated peptide region determines the ability of the proprotein convertase furin to cleave tgf-βs. J. Cell. Biochem. 2008, 103, 311–320. [Google Scholar] [CrossRef]
- Dubois, C.M.; Laprise, M.H.; Blanchette, F.; Gentry, L.E.; Leduc, R. Processing of transforming growth factor beta 1 precursor by human furin convertase. J. Biol. Chem. 1995, 270, 10618–10624. [Google Scholar] [CrossRef] [Green Version]
- Anderson, E.N.; Wharton, K.A. Alternative cleavage of the bone morphogenetic protein (bmp), gbb, produces ligands with distinct developmental functions and receptor preferences. J. Biol. Chem. 2017, 292, 19160–19178. [Google Scholar] [CrossRef] [Green Version]
- Annes, J.P.; Munger, J.S.; Rifkin, D.B. Making sense of latent tgfβ activation. J. Cell Sci. 2003, 116, 217–224. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sengle, G.; Charbonneau, N.L.; Ono, R.N.; Sasaki, T.; Alvarez, J.; Keene, D.R.; Bächinger, H.P.; Sakai, L.Y. Targeting of bone morphogenetic protein growth factor complexes to fibrillin. J. Biol. Chem. 2008, 283, 13874–13888. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Walsh, D.W.; Godson, C.; Brazil, D.P.; Martin, F. Extracellular bmp-antagonist regulation in development and disease: Tied up in knots. Trends Cell Biol. 2010, 20, 244–256. [Google Scholar] [CrossRef] [PubMed]
- Annes, J.P.; Chen, Y.; Munger, J.S.; Rifkin, D.B. Integrin alphavbeta6-mediated activation of latent tgf-beta requires the latent tgf-beta binding protein-1. J. Cell Biol. 2004, 165, 723–734. [Google Scholar] [CrossRef] [PubMed]
- Dallas, S.L.; Sivakumar, P.; Jones, C.J.; Chen, Q.; Peters, D.M.; Mosher, D.F.; Humphries, M.J.; Kielty, C.M. Fibronectin regulates latent transforming growth factor-beta (tgf beta) by controlling matrix assembly of latent tgf beta-binding protein-1. J. Biol. Chem. 2005, 280, 18871–18880. [Google Scholar] [CrossRef] [Green Version]
- Robertson, I.B.; Horiguchi, M.; Zilberberg, L.; Dabovic, B.; Hadjiolova, K.; Rifkin, D.B. Latent tgf-β-binding proteins. Matrix Biol. 2015, 47, 44–53. [Google Scholar] [CrossRef]
- Lopez-Dee, Z.; Pidcock, K.; Gutierrez, L.S. Thrombospondin-1: Multiple paths to inflammation. Mediat. Inflamm. 2011, 2011, 296069. [Google Scholar] [CrossRef] [Green Version]
- Schultz-Cherry, S.; Murphy-Ullrich, J.E. Thrombospondin causes activation of latent transforming growth factor-beta secreted by endothelial cells by a novel mechanism. J. Cell Biol. 1993, 122, 923–932. [Google Scholar] [CrossRef] [Green Version]
- Roberts, A.B.; Sporn, M.B.; Assoian, R.K.; Smith, J.M.; Roche, N.S.; Wakefield, L.M.; Heine, U.I.; Liotta, L.A.; Falanga, V.; Kehrl, J.H.; et al. Transforming growth factor type beta: Rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc. Natl. Acad. Sci. USA 1986, 83, 4167–4171. [Google Scholar] [CrossRef] [Green Version]
- Zugmaier, G.; Paik, S.; Wilding, G.; Knabbe, C.; Bano, M.; Lupu, R.; Deschauer, B.; Simpson, S.; Dickson, R.B.; Lippman, M. Transforming growth factor beta 1 induces cachexia and systemic fibrosis without an antitumor effect in nude mice. Cancer Res. 1991, 51, 3590–3594. [Google Scholar]
- Terrell, T.G.; Working, P.K.; Chow, C.P.; Green, J.D. Pathology of recombinant human transforming growth factor-beta 1 in rats and rabbits. Int. Rev. Exp. Pathol. 1993, 34 Pt B, 43–67. [Google Scholar]
- Lee, C.G.; Kang, H.-R.; Homer, R.J.; Chupp, G.; Elias, J.A. Transgenic modeling of transforming growth factor-beta(1): Role of apoptosis in fibrosis and alveolar remodeling. Proc. Am. Thorac. Soc. 2006, 3, 418–423. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Böttinger, E.P.; Letterio, J.J.; Roberts, A.B. Biology of tgf-β in knockout and transgenic mouse models. Kidney Int. 1997, 51, 1355–1360. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Border, W.A.; Okuda, S.; Languino, L.R.; Sporn, M.B.; Ruoslahti, E. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor beta 1. Nature 1990, 346, 371–374. [Google Scholar] [CrossRef] [PubMed]
- Border, W.A.; Noble, N.A.; Yamamoto, T.; Harper, J.R.; Yamaguchi, Y.; Pierschbacher, M.D.; Ruoslahti, E. Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease. Nature 1992, 360, 361–364. [Google Scholar] [CrossRef] [PubMed]
- Verrecchia, F.; Chu, M.L.; Mauviel, A. Identification of novel tgf-beta /smad gene targets in dermal fibroblasts using a combined cdna microarray/promoter transactivation approach. J. Biol. Chem. 2001, 276, 17058–17062. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ma, J.; Sanchez-Duffhues, G.; Goumans, M.J.; Ten Dijke, P. Tgf-β-induced endothelial to mesenchymal transition in disease and tissue engineering. Front. Cell Dev. Biol. 2020, 8, 260. [Google Scholar] [CrossRef]
- Carthy, J.M. Tgfβ signaling and the control of myofibroblast differentiation: Implications for chronic inflammatory disorders. J. Cell Physiol. 2018, 233, 98–106. [Google Scholar] [CrossRef] [Green Version]
- Klingberg, F.; Hinz, B.; White, E.S. The myofibroblast matrix: Implications for tissue repair and fibrosis. J. Pathol. 2013, 229, 298–309. [Google Scholar] [CrossRef] [Green Version]
- Zent, J.; Guo, L.W. Signaling mechanisms of myofibroblastic activation: Outside-in and inside-out. Cell. Physiol. Biochem. 2018, 49, 848–868. [Google Scholar] [CrossRef]
- Dobaczewski, M.; Bujak, M.; Li, N.; Gonzalez-Quesada, C.; Mendoza, L.H.; Wang, X.F.; Frangogiannis, N.G. Smad3 signaling critically regulates fibroblast phenotype and function in healing myocardial infarction. Circ. Res. 2010, 107, 418–428. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Desmoulière, A.; Redard, M.; Darby, I.; Gabbiani, G. Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am. J. Pathol. 1995, 146, 56–66. [Google Scholar] [PubMed]
- Hinz, B.; Phan, S.H.; Thannickal, V.J.; Galli, A.; Bochaton-Piallat, M.L.; Gabbiani, G. The myofibroblast: One function, multiple origins. Am. J. Pathol. 2007, 170, 1807–1816. [Google Scholar] [CrossRef] [PubMed]
- Hinz, B.; Celetta, G.; Tomasek, J.J.; Gabbiani, G.; Chaponnier, C. Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. Mol. Biol. Cell 2001, 12, 2730–2741. [Google Scholar] [CrossRef] [Green Version]
- Tomasek, J.J.; Gabbiani, G.; Hinz, B.; Chaponnier, C.; Brown, R.A. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat. Rev. Mol. Cell Biol. 2002, 3, 349–363. [Google Scholar] [CrossRef]
- Hinz, B. The myofibroblast: Paradigm for a mechanically active cell. J. Biomech. 2010, 43, 146–155. [Google Scholar] [CrossRef]
- Chambers, R.C.; Leoni, P.; Kaminski, N.; Laurent, G.J.; Heller, R.A. Global expression profiling of fibroblast responses to transforming growth factor-beta1 reveals the induction of inhibitor of differentiation-1 and provides evidence of smooth muscle cell phenotypic switching. Am. J. Pathol. 2003, 162, 533–546. [Google Scholar] [CrossRef]
- Hinz, B. Masters and servants of the force: The role of matrix adhesions in myofibroblast force perception and transmission. Eur. J. Cell Biol. 2006, 85, 175–181. [Google Scholar] [CrossRef]
- Wipff, P.-J.; Rifkin, D.B.; Meister, J.-J.; Hinz, B. Myofibroblast contraction activates latent tgf-beta1 from the extracellular matrix. J. Cell Biol. 2007, 179, 1311–1323. [Google Scholar] [CrossRef] [Green Version]
- Sarrazy, V.; Koehler, A.; Chow, M.L.; Zimina, E.; Li, C.X.; Kato, H.; Caldarone, C.A.; Hinz, B. Integrins αvβ5 and αvβ3 promote latent tgf-β1 activation by human cardiac fibroblast contraction. Cardiovasc. Res. 2014, 102, 407–417. [Google Scholar] [CrossRef] [Green Version]
- Rock, J.R.; Barkauskas, C.E.; Cronce, M.J.; Xue, Y.; Harris, J.R.; Liang, J.; Noble, P.W.; Hogan, B.L.M. Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition. Proc. Natl. Acad. Sci. USA 2011, 108, E1475–E1483. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tsukui, T.; Sun, K.-H.; Wetter, J.B.; Wilson-Kanamori, J.R.; Hazelwood, L.A.; Henderson, N.C.; Adams, T.S.; Schupp, J.C.; Poli, S.D.; Rosas, I.O.; et al. Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis. Nat. Commun. 2020, 11, 1920. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, K.-H.; Chang, Y.; Reed, N.I.; Sheppard, D. Α-smooth muscle actin is an inconsistent marker of fibroblasts responsible for force-dependent tgfβ activation or collagen production across multiple models of organ fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol. 2016, 310, L824–L836. [Google Scholar] [CrossRef] [Green Version]
- Guerrero-Juarez, C.F.; Dedhia, P.H.; Jin, S.; Ruiz-Vega, R.; Ma, D.; Liu, Y.; Yamaga, K.; Shestova, O.; Gay, D.L.; Yang, Z.; et al. Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds. Nat. Commun. 2019, 10, 650. [Google Scholar] [CrossRef] [PubMed]
- Xie, T.; Wang, Y.; Deng, N.; Huang, G.; Taghavifar, F.; Geng, Y.; Liu, N.; Kulur, V.; Yao, C.; Chen, P.; et al. Single-cell deconvolution of fibroblast heterogeneity in mouse pulmonary fibrosis. Cell Rep. 2018, 22, 3625–3640. [Google Scholar] [CrossRef] [Green Version]
- Binks, A.P.; Beyer, M.; Miller, R.; LeClair, R.J. Cthrc1 lowers pulmonary collagen associated with bleomycin-induced fibrosis and protects lung function. Physiol. Rep. 2017, 5, e13115. [Google Scholar] [CrossRef] [PubMed]
- Bian, Z.; Miao, Q.; Zhong, W.; Zhang, H.; Wang, Q.; Peng, Y.; Chen, X.; Guo, C.; Shen, L.; Yang, F.; et al. Treatment of cholestatic fibrosis by altering gene expression of cthrc1: Implications for autoimmune and non-autoimmune liver disease. J. Autoimmun. 2015, 63, 76–87. [Google Scholar] [CrossRef] [Green Version]
- Zhao, M.-j.; Chen, S.-y.; Qu, X.-y.; Abdul-fattah, B.; Lai, T.; Xie, M.; Wu, S.-d.; Zhou, Y.-w.; Huang, C.-z. Increased cthrc1 activates normal fibroblasts and suppresses keloid fibroblasts by inhibiting tgf-β/smad signal pathway and modulating yap subcellular location. Curr. Med. Sci. 2018, 38, 894–902. [Google Scholar] [CrossRef]
- LeClair, R.J.; Durmus, T.; Wang, Q.; Pyagay, P.; Terzic, A.; Lindner, V. Cthrc1 is a novel inhibitor of transforming growth factor-beta signaling and neointimal lesion formation. Circ. Res. 2007, 100, 826–833. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, J.; Wang, Y.; Ma, M.; Jiang, S.; Zhang, X.; Zhang, Y.; Yang, X.; Xu, C.; Tian, G.; Li, Q.; et al. Autocrine cthrc1 activates hepatic stellate cells and promotes liver fibrosis by activating tgf-β signaling. EBioMedicine 2019, 40, 43–55. [Google Scholar] [CrossRef] [Green Version]
- Kamath, V.V.; Krishnamurthy, S.; Satelur, K.P.; Rajkumar, K. Transforming growth factor-β1 and tgf-β2 act synergistically in the fibrotic pathway in oral submucous fibrosis: An immunohistochemical observation. Indian J. Med. Paediatr. Oncol. 2015, 36, 111–116. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wordinger, R.J.; Sharma, T.; Clark, A.F. The role of tgf-β2 and bone morphogenetic proteins in the trabecular meshwork and glaucoma. J. Ocul. Pharmacol. Ther. 2014, 30, 154–162. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abd el-Meguid, M.; Dawood, R.M.; Mokhles, M.A.; El Awady, M.K. Extrahepatic upregulation of transforming growth factor beta 2 in hcv genotype 4-induced liver fibrosis. J. Interferon Cytokine Res. 2018, 38, 341–347. [Google Scholar] [CrossRef] [PubMed]
- Shah, M.; Foreman, D.M.; Ferguson, M.W. Neutralisation of tgf-beta 1 and tgf-beta 2 or exogenous addition of tgf-beta 3 to cutaneous rat wounds reduces scarring. J. Cell Sci. 1995, 108, 985–1002. [Google Scholar]
- Chang, Z.; Kishimoto, Y.; Hasan, A.; Welham, N.V. Tgf-β3 modulates the inflammatory environment and reduces scar formation following vocal fold mucosal injury in rats. Dis. Models Mech. 2014, 7, 83–91. [Google Scholar] [CrossRef] [Green Version]
- Hosokawa, R.; Nonaka, K.; Morifuji, M.; Shum, L.; Ohishi, M. Tgf-beta 3 decreases type i collagen and scarring after labioplasty. J. Dent. Res. 2003, 82, 558–564. [Google Scholar] [CrossRef]
- Walton, K.L.; Johnson, K.E.; Harrison, C.A. Targeting tgf-beta mediated smad signaling for the prevention of fibrosis. Front. Pharmacol. 2017, 8, 461. [Google Scholar] [CrossRef] [Green Version]
- Ozkaynak, E.; Schnegelsberg, P.N.; Oppermann, H. Murine osteogenic protein (op-1): High levels of mrna in kidney. Biochem. Biophys. Res. Commun. 1991, 179, 116–123. [Google Scholar] [CrossRef]
- Izumi, M.; Watanabe, M.; Sawaki, K.; Yamaguchi, H.; Kawaguchi, M. Expression of bmp7 is associated with resistance to diabetic stress: Comparison among mouse salivary glands. Eur. J. Pharm. 2008, 596, 1–5. [Google Scholar] [CrossRef] [Green Version]
- Wang, S.N.; Lapage, J.; Hirschberg, R. Loss of tubular bone morphogenetic protein-7 in diabetic nephropathy. J. Am. Soc. Nephrol. 2001, 12, 2392–2399. [Google Scholar]
- Sugimoto, H.; LeBleu, V.S.; Bosukonda, D.; Keck, P.; Taduri, G.; Bechtel, W.; Okada, H.; Carlson, W., Jr.; Bey, P.; Rusckowski, M.; et al. Activin-like kinase 3 is important for kidney regeneration and reversal of fibrosis. Nat. Med. 2012, 18, 396–404. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, Y.L.; Liu, Y.S.; Chuang, L.Y.; Guh, J.Y.; Lee, T.C.; Liao, T.N.; Hung, M.Y.; Chiang, T.A. Bone morphogenetic protein-2 antagonizes renal interstitial fibrosis by promoting catabolism of type i transforming growth factor-beta receptors. Endocrinology 2009, 150, 727–740. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dendooven, A.; van Oostrom, O.; van der Giezen, D.M.; Leeuwis, J.W.; Snijckers, C.; Joles, J.A.; Robertson, E.J.; Verhaar, M.C.; Nguyen, T.Q.; Goldschmeding, R. Loss of endogenous bone morphogenetic protein-6 aggravates renal fibrosis. Am. J. Pathol. 2011, 178, 1069–1079. [Google Scholar] [CrossRef]
- Arndt, S.; Wacker, E.; Dorn, C.; Koch, A.; Saugspier, M.; Thasler, W.E.; Hartmann, A.; Bosserhoff, A.K.; Hellerbrand, C. Enhanced expression of bmp6 inhibits hepatic fibrosis in non-alcoholic fatty liver disease. Gut 2015, 64, 973–981. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chung, Y.H.; Huang, Y.H.; Chu, T.H.; Chen, C.L.; Lin, P.R.; Huang, S.C.; Wu, D.C.; Huang, C.C.; Hu, T.H.; Kao, Y.H.; et al. Bmp-2 restoration aids in recovery from liver fibrosis by attenuating tgf-β1 signaling. Lab. Investig. 2018, 98, 999–1013. [Google Scholar] [CrossRef] [Green Version]
- Arndt, S.; Karrer, S.; Hellerbrand, C.; Bosserhoff, A.K. Bone morphogenetic protein-6 inhibits fibrogenesis in scleroderma offering treatment options for fibrotic skin disease. J. Investig. Dermatol. 2019, 139, 1914–1924.e1916. [Google Scholar] [CrossRef] [PubMed]
- Zhong, L.; Wang, X.; Wang, S.; Yang, L.; Gao, H.; Yang, C. The anti-fibrotic effect of bone morphogenic protein-7(bmp-7) on liver fibrosis. Int. J. Med. Sci. 2013, 10, 441–450. [Google Scholar] [CrossRef] [Green Version]
- Pegorier, S.; Campbell, G.A.; Kay, A.B.; Lloyd, C.M. Bone morphogenetic protein (bmp)-4 and bmp-7 regulate differentially transforming growth factor (tgf)-beta1 in normal human lung fibroblasts (nhlf). Respir. Res. 2010, 11, 85. [Google Scholar] [CrossRef] [Green Version]
- Fan, J.; Shen, H.; Sun, Y.; Li, P.; Burczynski, F.; Namaka, M.; Gong, Y. Bone morphogenetic protein 4 mediates bile duct ligation induced liver fibrosis through activation of smad1 and erk1/2 in rat hepatic stellate cells. J. Cell. Physiol. 2006, 207, 499–505. [Google Scholar] [CrossRef]
- Sun, B.; Huo, R.; Sheng, Y.; Li, Y.; Xie, X.; Chen, C.; Liu, H.B.; Li, N.; Li, C.B.; Guo, W.T.; et al. Bone morphogenetic protein-4 mediates cardiac hypertrophy, apoptosis, and fibrosis in experimentally pathological cardiac hypertrophy. Hypertension 2013, 61, 352–360. [Google Scholar] [CrossRef] [Green Version]
- Yao, H.; Li, H.; Yang, S.; Li, M.; Zhao, C.; Zhang, J.; Xu, G.; Wang, F. Inhibitory effect of bone morphogenetic protein 4 in retinal pigment epithelial-mesenchymal transition. Sci. Rep. 2016, 6, 32182. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.L.; Ju, H.Z.; Liu, S.F.; Lee, T.C.; Shih, Y.W.; Chuang, L.Y.; Guh, J.Y.; Yang, Y.Y.; Liao, T.N.; Hung, T.J.; et al. Bmp-2 suppresses renal interstitial fibrosis by regulating epithelial-mesenchymal transition. J. Cell Biochem. 2011, 112, 2558–2565. [Google Scholar] [CrossRef] [PubMed]
- Loureiro, J.; Schilte, M.; Aguilera, A.; Albar-Vizcaíno, P.; Ramírez-Huesca, M.; Pérez-Lozano, M.L.; González-Mateo, G.; Aroeira, L.S.; Selgas, R.; Mendoza, L.; et al. Bmp-7 blocks mesenchymal conversion of mesothelial cells and prevents peritoneal damage induced by dialysis fluid exposure. Nephrol. Dial. Transpl. 2010, 25, 1098–1108. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, S.; Hirschberg, R. Bmp7 antagonizes tgf-beta -dependent fibrogenesis in mesangial cells. Am. J. Physiol. Ren. Physiol. 2003, 284, F1006–F1013. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zeisberg, M.; Hanai, J.; Sugimoto, H.; Mammoto, T.; Charytan, D.; Strutz, F.; Kalluri, R. Bmp-7 counteracts tgf-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat. Med. 2003, 9, 964–968. [Google Scholar] [CrossRef]
- Dituri, F.; Cossu, C.; Mancarella, S.; Giannelli, G. The interactivity between tgfβ and bmp signaling in organogenesis, fibrosis, and cancer. Cells 2019, 8, 1130. [Google Scholar] [CrossRef] [Green Version]
- Lafyatis, R. Transforming growth factor β—At the centre of systemic sclerosis. Nat. Rev. Rheumatol. 2014, 10, 706–719. [Google Scholar] [CrossRef]
- Zhang, T.; Wang, X.F.; Wang, Z.C.; Lou, D.; Fang, Q.Q.; Hu, Y.Y.; Zhao, W.Y.; Zhang, L.Y.; Wu, L.H.; Tan, W.Q. Current potential therapeutic strategies targeting the tgf-β/smad signaling pathway to attenuate keloid and hypertrophic scar formation. Biomed. Pharm. 2020, 129, 110287. [Google Scholar] [CrossRef]
- Fernandez, I.E.; Eickelberg, O. The impact of tgf-β on lung fibrosis: From targeting to biomarkers. Proc. Am. Thorac. Soc. 2012, 9, 111–116. [Google Scholar] [CrossRef]
- Fabregat, I.; Moreno-Càceres, J.; Sánchez, A.; Dooley, S.; Dewidar, B.; Giannelli, G.; Ten Dijke, P. Tgf-β signalling and liver disease. FEBS J. 2016, 283, 2219–2232. [Google Scholar] [CrossRef] [Green Version]
- Isaka, Y. Targeting tgf-β signaling in kidney fibrosis. Int. J. Mol. Sci. 2018, 19, 2532. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Leask, A. Tgfβ, cardiac fibroblasts, and the fibrotic response. Cardiovasc. Res. 2007, 74, 207–212. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Burks, T.N.; Cohn, R.D. Role of tgf-β signaling in inherited and acquired myopathies. Skelet. Muscle 2011, 1, 19. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hall, B.E.; Zheng, C.; Swaim, W.D.; Cho, A.; Nagineni, C.N.; Eckhaus, M.A.; Flanders, K.C.; Ambudkar, I.S.; Baum, B.J.; Kulkarni, A.B. Conditional overexpression of tgf-beta1 disrupts mouse salivary gland development and function. Lab. Investig. 2010, 90, 543–555. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Leehan, K.M.; Pezant, N.P.; Rasmussen, A.; Grundahl, K.; Moore, J.S.; Radfar, L.; Lewis, D.M.; Stone, D.U.; Lessard, C.J.; Rhodus, N.L.; et al. Minor salivary gland fibrosis in sjögren’s syndrome is elevated, associated with focus score and not solely a consequence of aging. Clin. Exp. Rheumatol. 2018, 36 (Suppl. 112), 80–88. [Google Scholar]
- Teymoortash, A.; Tiemann, M.; Schrader, C.; Hartmann, O.; Werner, J.A. Transforming growth factor beta in chronic obstructive sialadenitis of human submandibular gland. Arch. Oral Biol. 2003, 48, 111–116. [Google Scholar] [CrossRef]
- Kizu, Y.; Sakurai, H.; Katagiri, S.; Shinozaki, N.; Ono, M.; Tsubota, K.; Saito, J. Immunohistological analysis of tumour growth factor beta 1 expression in normal and inflamed salivary glands. J. Clin. Pathol. 1996, 49, 728–732. [Google Scholar] [CrossRef] [Green Version]
- Takahashi, D.; Suzuki, H.; Kakei, Y.; Yamakoshi, K.; Minami, Y.; Komori, T.; Nishita, M. Expression of ror2 associated with fibrosis of the submandibular gland. Cell Struct. Funct. 2017, 42, 159–167. [Google Scholar] [CrossRef]
- Woods, L.T.; Camden, J.M.; El-Sayed, F.G.; Khalafalla, M.G.; Petris, M.J.; Erb, L.; Weisman, G.A. Increased expression of tgf-β signaling components in a mouse model of fibrosis induced by submandibular gland duct ligation. PLoS ONE 2015, 10, e0123641. [Google Scholar] [CrossRef] [Green Version]
- Arias, M.; Sauer-Lehnen, S.; Treptau, J.; Janoschek, N.; Theuerkauf, I.; Buettner, R.; Gressner, A.M.; Weiskirchen, R. Adenoviral expression of a transforming growth factor-beta1 antisense mrna is effective in preventing liver fibrosis in bile-duct ligated rats. BMC Gastroenterol. 2003, 3, 29. [Google Scholar] [CrossRef] [Green Version]
- Wang, B.; Dolinski, B.M.; Kikuchi, N.; Leone, D.R.; Peters, M.G.; Weinreb, P.H.; Violette, S.M.; Bissell, D.M. Role of alphavbeta6 integrin in acute biliary fibrosis. Hepatology 2007, 46, 1404–1412. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dirix, P.; Nuyts, S.; Van den Bogaert, W. Radiation-induced xerostomia in patients with head and neck cancer: A literature review. Cancer 2006, 107, 2525–2534. [Google Scholar] [CrossRef] [PubMed]
- Anscher, M.S.; Kong, F.M.; Murase, T.; Jirtle, R.L. Short communication: Normal tissue injury after cancer therapy is a local response exacerbated by an endocrine effect of tgf beta. Br. J. Radiol. 1995, 68, 331–333. [Google Scholar] [CrossRef] [PubMed]
- Hakim, S.G.; Ribbat, J.; Berndt, A.; Richter, P.; Kosmehl, H.; Benedek, G.A.; Jacobsen, H.C.; Trenkle, T.; Sieg, P.; Rades, D. Expression of wnt-1, tgf-β and related cell-cell adhesion components following radiotherapy in salivary glands of patients with manifested radiogenic xerostomia. Radiother. Oncol. 2011, 101, 93–99. [Google Scholar] [CrossRef]
- Spiegelberg, L.; Swagemakers, S.M.A.; van Ijcken, W.F.J.; Oole, E.; Wolvius, E.B.; Essers, J.; Braks, J.A.M. Gene expression analysis reveals inhibition of radiation-induced tgf beta-signaling by hyperbaric oxygen therapy in mouse salivary glands. Mol. Med. 2014, 20, 257–269. [Google Scholar] [CrossRef]
- Theander, E.; Jacobsson, L.T.H. Relationship of sjögren’s syndrome to other connective tissue and autoimmune disorders. Rheum. Dis. Clin. 2008, 34, 935–947. [Google Scholar] [CrossRef]
- Shiboski, C.H.; Shiboski, S.C.; Seror, R.; Criswell, L.A.; Labetoulle, M.; Lietman, T.M.; Rasmussen, A.; Scofield, H.; Vitali, C.; Bowman, S.J.; et al. 2016 american college of rheumatology/european league against rheumatism classification criteria for primary sjögren’s syndrome: A consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol. 2017, 69, 35–45. [Google Scholar] [CrossRef]
- Shull, M.M.; Ormsby, I.; Kier, A.B.; Pawlowski, S.; Diebold, R.J.; Yin, M.; Allen, R.; Sidman, C.; Proetzel, G.; Calvin, D.; et al. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 1992, 359, 693–699. [Google Scholar] [CrossRef]
- Boivin, G.P.; O’Toole, B.A.; Orsmby, I.E.; Diebold, R.J.; Eis, M.J.; Doetschman, T.; Kier, A.B. Onset and progression of pathological lesions in transforming growth factor-beta 1-deficient mice. Am. J. Pathol. 1995, 146, 276–288. [Google Scholar]
- Kim, D.; Kim, J.Y.; Jun, H.-S. Smad4 in t cells plays a protective role in the development of autoimmune sjögren’s syndrome in the nonobese diabetic mouse. Oncotarget 2016, 7, 80298–80312. [Google Scholar] [CrossRef] [Green Version]
- Dang, H.; Geiser, A.G.; Letterio, J.J.; Nakabayashi, T.; Kong, L.; Fernandes, G.; Talal, N. Sle-like autoantibodies and sjögren’s syndrome-like lymphoproliferation in tgf-beta knockout mice. J. Immunol. 1995, 155, 3205–3212. [Google Scholar] [PubMed]
- Cozzani, E.; Drosera, M.; Gasparini, G.; Parodi, A. Serology of lupus erythematosus: Correlation between immunopathological features and clinical aspects. Autoimmune Dis. 2014, 2014, 321359. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Franceschini, F.; Cavazzana, I. Anti-ro/ssa and la/ssb antibodies. Autoimmunity 2005, 38, 55–63. [Google Scholar] [CrossRef] [PubMed]
- Rubtsov, Y.P.; Rudensky, A.Y. Tgfβ signalling in control of t-cell-mediated self-reactivity. Nat. Rev. Immunol. 2007, 7, 443–453. [Google Scholar] [CrossRef]
- Chen, W.; Jin, W.; Hardegen, N.; Lei, K.-J.; Li, L.; Marinos, N.; McGrady, G.; Wahl, S.M. Conversion of peripheral cd4+cd25− naive t cells to cd4+cd25+ regulatory t cells by tgf-β induction of transcription factor foxp3. J. Exp. Med. 2003, 198, 1875–1886. [Google Scholar] [CrossRef]
- Davidson, T.S.; DiPaolo, R.J.; Andersson, J.; Shevach, E.M. Cutting edge: Il-2 is essential for tgf-β-mediated induction of foxp3+ t regulatory cells. J. Immunol. 2007, 178, 4022–4026. [Google Scholar] [CrossRef] [Green Version]
- Zheng, S.G.; Wang, J.; Wang, P.; Gray, J.D.; Horwitz, D.A. Il-2 is essential for tgf-β to convert naive cd4+cd25− cells to cd25+foxp3+ regulatory t cells and for expansion of these cells. J. Immunol. 2007, 178, 2018–2027. [Google Scholar] [CrossRef] [Green Version]
- Bettelli, E.; Carrier, Y.; Gao, W.; Korn, T.; Strom, T.B.; Oukka, M.; Weiner, H.L.; Kuchroo, V.K. Reciprocal developmental pathways for the generation of pathogenic effector th17 and regulatory t cells. Nature 2006, 441, 235–238. [Google Scholar] [CrossRef]
- Prud’homme, G.J. Pathobiology of transforming growth factor β in cancer, fibrosis and immunologic disease, and therapeutic considerations. Lab. Investig. 2007, 87, 1077–1091. [Google Scholar] [CrossRef] [Green Version]
- Li, M.O.; Wan, Y.Y.; Flavell, R.A. T cell-produced transforming growth factor-beta1 controls t cell tolerance and regulates th1- and th17-cell differentiation. Immunity 2007, 26, 579–591. [Google Scholar] [CrossRef] [Green Version]
- Yao, Y.; Ma, J.-F.; Chang, C.; Xu, T.; Gao, C.-Y.; Gershwin, M.E.; Lian, Z.-X. Immunobiology of t cells in sjögren’s syndrome. Clin. Rev. Allergy Immunol. 2020. [Google Scholar] [CrossRef] [PubMed]
- Lai, Z.; Yin, H.; Cabrera-Pérez, J.; Guimaro, M.C.; Afione, S.; Michael, D.G.; Glenton, P.; Patel, A.; Swaim, W.D.; Zheng, C.; et al. Aquaporin gene therapy corrects sjögren’s syndrome phenotype in mice. Proc. Natl. Acad. Sci. USA 2016, 113, 5694–5699. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yin, H.; Cabrera-Perez, J.; Lai, Z.; Michael, D.; Weller, M.; Swaim, W.D.; Liu, X.; Catalán, M.A.; Rocha, E.M.; Ismail, N.; et al. Association of bone morphogenetic protein 6 with exocrine gland dysfunction in patients with sjögren’s syndrome and in mice. Arthritis Rheum. 2013, 65, 3228–3238. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yin, H.; Kalra, L.; Lai, Z.; Guimaro, M.C.; Aber, L.; Warner, B.M.; Michael, D.; Zhang, N.; Cabrera-Perez, J.; Karim, A.; et al. Inhibition of bone morphogenetic protein 6 receptors ameliorates sjögren’s syndrome in mice. Sci. Rep. 2020, 10, 2967. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, J.; Su, Y.; Hu, L.; Cain, A.; Gu, Y.; Liu, B.; Wu, R.; Wang, S.; Wang, H. Effect of bone morphogenetic protein 6 on immunomodulatory functions of salivary gland-derived mesenchymal stem cells in sjögren’s syndrome. Stem Cells Dev. 2018, 27, 1540–1548. [Google Scholar] [CrossRef] [PubMed]
- Aqrawi, L.A.; Galtung, H.K.; Guerreiro, E.M.; Øvstebø, R.; Thiede, B.; Utheim, T.P.; Chen, X.; Utheim, Ø.A.; Palm, Ø.; Skarstein, K.; et al. Proteomic and histopathological characterisation of sicca subjects and primary sjögren’s syndrome patients reveals promising tear, saliva and extracellular vesicle disease biomarkers. Arthritis Res. Therapy 2019, 21, 181. [Google Scholar]
- Saxena, V.; Lienesch, D.W.; Zhou, M.; Bommireddy, R.; Azhar, M.; Doetschman, T.; Singh, R.R. Dual roles of immunoregulatory cytokine tgf-beta in the pathogenesis of autoimmunity-mediated organ damage. J. Immunol. (Baltim. Md. 1950) 2008, 180, 1903–1912. [Google Scholar] [CrossRef] [Green Version]
- Sisto, M.; Lorusso, L.; Tamma, R.; Ingravallo, G.; Ribatti, D.; Lisi, S. Interleukin-17 and -22 synergy linking inflammation and emt-dependent fibrosis in sjögren’s syndrome. Clin. Exp. Immunol. 2019, 198, 261–272. [Google Scholar] [CrossRef]
- Sisto, M.; Lorusso, L.; Ingravallo, G.; Tamma, R.; Ribatti, D.; Lisi, S. The tgf-β1 signaling pathway as an attractive target in the fibrosis pathogenesis of sjögren’s syndrome. Mediat. Inflamm. 2018, 2018, 1965935. [Google Scholar] [CrossRef] [Green Version]
- Ohta, N.; Kurakami, K.; Ishida, A.; Furukawa, T.; Suzuki, Y.; Aoyagi, M.; Matsubara, A.; Lzuhara, K.; Kakehata, S. Roles of tgf-beta and periostin in fibrosclerosis in patients with igg4-related diseases. Acta Oto-Laryngol. 2013, 133, 1322–1327. [Google Scholar] [CrossRef]
- Yajima, R.; Takano, K.; Konno, T.; Kohno, T.; Kaneko, Y.; Kakuki, T.; Nomura, K.; Kakiuchi, A.; Himi, T.; Kojima, T. Mechanism of fibrogenesis in submandibular glands in patients with igg4-rd. J. Mol. Histol. 2018, 49, 577–587. [Google Scholar] [CrossRef] [PubMed]
- Muñoz-Félix, J.M.; González-Núñez, M.; Martínez-Salgado, C.; López-Novoa, J.M. Tgf-β/bmp proteins as therapeutic targets in renal fibrosis. Where have we arrived after 25 years of trials and tribulations? Pharmcol. Ther. 2015, 156, 44–58. [Google Scholar] [CrossRef] [PubMed]
- Hawinkels, L.J.; Ten Dijke, P. Exploring anti-tgf-β therapies in cancer and fibrosis. Growth Factors 2011, 29, 140–152. [Google Scholar] [CrossRef] [PubMed]
- Varga, J.; Pasche, B. Antitransforming growth factor-beta therapy in fibrosis: Recent progress and implications for systemic sclerosis. Curr. Opin. Rheumatol. 2008, 20, 720–728. [Google Scholar] [CrossRef] [Green Version]
- Horan, G.S.; Wood, S.; Ona, V.; Li, D.J.; Lukashev, M.E.; Weinreb, P.H.; Simon, K.J.; Hahm, K.; Allaire, N.E.; Rinaldi, N.J.; et al. Partial inhibition of integrin alpha(v)beta6 prevents pulmonary fibrosis without exacerbating inflammation. Am. J. Respir. Crit. Care Med. 2008, 177, 56–65. [Google Scholar] [CrossRef] [PubMed]
- Liu, W.; Sun, T.; Wang, Y. Integrin αvβ6 mediates epithelial-mesenchymal transition in human bronchial epithelial cells induced by lipopolysaccharides of pseudomonas aeruginosa via tgf-β1-smad2/3 signaling pathway. Folia Microbiol. (Praha) 2020, 65, 329–338. [Google Scholar] [CrossRef] [Green Version]
- Arefayene, M.; Mouded, M.; Stebbins, C.; Zhao, G.; Song, G.; Christmann, R.; Violette, S.; Gallagher, D. Phase 2b dose selection of bg00011 for the treatment of idiopathic pulmonary fibrosis (ipf). Eur. Respir. J. 2018, 52, PA596. [Google Scholar]
- Maden, C.H.; Fairman, D.; Chalker, M.; Costa, M.J.; Fahy, W.A.; Garman, N.; Lukey, P.T.; Mant, T.; Parry, S.; Simpson, J.K.; et al. Safety, tolerability and pharmacokinetics of gsk3008348, a novel integrin αvβ6 inhibitor, in healthy participants. Eur. J. Clin. Pharm. 2018, 74, 701–709. [Google Scholar] [CrossRef]
- Cottin, V.; Koschel, D.; Günther, A.; Albera, C.; Azuma, A.; Sköld, C.M.; Tomassetti, S.; Hormel, P.; Stauffer, J.L.; Strombom, I.; et al. Long-term safety of pirfenidone: Results of the prospective, observational passport study. ERJ Open Res. 2018, 4, 00084–02018. [Google Scholar] [CrossRef]
- Sharma, K.; Ix, J.H.; Mathew, A.V.; Cho, M.; Pflueger, A.; Dunn, S.R.; Francos, B.; Sharma, S.; Falkner, B.; McGowan, T.A.; et al. Pirfenidone for diabetic nephropathy. J. Am. Soc. Nephrol. 2011, 22, 1144–1151. [Google Scholar] [CrossRef]
- Cho, M.E.; Smith, D.C.; Branton, M.H.; Penzak, S.R.; Kopp, J.B. Pirfenidone slows renal function decline in patients with focal segmental glomerulosclerosis. Clin. J. Am. Soc. Nephrol. 2007, 2, 906–913. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vincenti, F.; Fervenza, F.C.; Campbell, K.N.; Diaz, M.; Gesualdo, L.; Nelson, P.; Praga, M.; Radhakrishnan, J.; Sellin, L.; Singh, A.; et al. A phase 2, double-blind, placebo-controlled, randomized study of fresolimumab in patients with steroid-resistant primary focal segmental glomerulosclerosis. Kidney Int. Rep. 2017, 2, 800–810. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rice, L.M.; Padilla, C.M.; McLaughlin, S.R.; Mathes, A.; Ziemek, J.; Goummih, S.; Nakerakanti, S.; York, M.; Farina, G.; Whitfield, M.L.; et al. Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients. J. Clin. Investig. 2015, 125, 2795–2807. [Google Scholar] [CrossRef] [PubMed]
- Denton, C.P.; Merkel, P.A.; Furst, D.E.; Khanna, D.; Emery, P.; Hsu, V.M.; Silliman, N.; Streisand, J.; Powell, J.; Akesson, A.; et al. Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: A multicenter, randomized, placebo-controlled phase i/ii trial of cat-192. Arthritis Rheum. 2007, 56, 323–333. [Google Scholar] [CrossRef]
- Voelker, J.; Berg, P.H.; Sheetz, M.; Duffin, K.; Shen, T.; Moser, B.; Greene, T.; Blumenthal, S.S.; Rychlik, I.; Yagil, Y.; et al. Anti-tgf-β1 antibody therapy in patients with diabetic nephropathy. J. Am. Soc. Nephrol. 2017, 28, 953–962. [Google Scholar] [CrossRef] [Green Version]
- Khaw, P.; Grehn, F.; Holló, G.; Overton, B.; Wilson, R.; Vogel, R.; Smith, Z. A phase iii study of subconjunctival human anti-transforming growth factor beta(2) monoclonal antibody (cat-152) to prevent scarring after first-time trabeculectomy. Ophthalmology 2007, 114, 1822–1830. [Google Scholar]
- Yamada, M.; Kuwano, K.; Maeyama, T.; Yoshimi, M.; Hamada, N.; Fukumoto, J.; Egashira, K.; Hiasa, K.; Takayama, K.; Nakanishi, Y. Gene transfer of soluble transforming growth factor type ii receptor by in vivo electroporation attenuates lung injury and fibrosis. J. Clin. Pathol. 2007, 60, 916–920. [Google Scholar] [CrossRef] [Green Version]
- Santiago, B.; Gutierrez-Cañas, I.; Dotor, J.; Palao, G.; Lasarte, J.J.; Ruiz, J.; Prieto, J.; Borrás-Cuesta, F.; Pablos, J.L. Topical application of a peptide inhibitor of transforming growth factor-beta1 ameliorates bleomycin-induced skin fibrosis. J. Investig. Derm. 2005, 125, 450–455. [Google Scholar] [CrossRef] [Green Version]
- Juárez, P.; Vilchis-Landeros, M.M.; Ponce-Coria, J.; Mendoza, V.; Hernández-Pando, R.; Bobadilla, N.A.; López-Casillas, F. Soluble betaglycan reduces renal damage progression in db/db mice. Am. J. Physiol Ren. Physiol. 2007, 292, F321–F329. [Google Scholar] [CrossRef] [Green Version]
- Petersen, M.; Thorikay, M.; Deckers, M.; van Dinther, M.; Grygielko, E.T.; Gellibert, F.; de Gouville, A.C.; Huet, S.; ten Dijke, P.; Laping, N.J. Oral administration of gw788388, an inhibitor of tgf-β type i and ii receptor kinases, decreases renal fibrosis. Kidney Int. 2008, 73, 705–715. [Google Scholar] [CrossRef] [Green Version]
- De Oliveira, F.L.; Araújo-Jorge, T.C.; de Souza, E.M.; de Oliveira, G.M.; Degrave, W.M.; Feige, J.J.; Bailly, S.; Waghabi, M.C. Oral administration of gw788388, an inhibitor of transforming growth factor beta signaling, prevents heart fibrosis in chagas disease. PLoS Negl. Trop. Dis. 2012, 6, e1696. [Google Scholar] [CrossRef] [PubMed]
- Grygielko, E.T.; Martin, W.M.; Tweed, C.; Thornton, P.; Harling, J.; Brooks, D.P.; Laping, N.J. Inhibition of gene markers of fibrosis with a novel inhibitor of transforming growth factor-beta type i receptor kinase in puromycin-induced nephritis. J. Pharm. Exp. 2005, 313, 943–951. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Smoktunowicz, N.; Alexander, R.E.; Franklin, L.; Williams, A.E.; Holman, B.; Mercer, P.F.; Jarai, G.; Scotton, C.J.; Chambers, R.C. The anti-fibrotic effect of inhibition of tgfβ-alk5 signalling in experimental pulmonary fibrosis in mice is attenuated in the presence of concurrent γ-herpesvirus infection. Dis. Model. Mech. 2015, 8, 1129–1139. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Occleston, N.L.; O’Kane, S.; Laverty, H.G.; Cooper, M.; Fairlamb, D.; Mason, T.; Bush, J.A.; Ferguson, M.W. Discovery and development of avotermin (recombinant human transforming growth factor beta 3): A new class of prophylactic therapeutic for the improvement of scarring. Wound Repair Regen 2011, 19 (Suppl. 1), s38–s48. [Google Scholar] [CrossRef]
- Weiskirchen, R.; Meurer, S.K. Bmp-7 counteracting tgf-beta1 activities in organ fibrosis. Front. Biosci. (Landmark Ed.) 2013, 18, 1407–1434. [Google Scholar] [CrossRef] [Green Version]
- Himmelfarb, J.; Chertow, G.M.; McCullough, P.A.; Mesana, T.; Shaw, A.D.; Sundt, T.M.; Brown, C.; Cortville, D.; Dagenais, F.; de Varennes, B.; et al. Perioperative thr-184 and aki after cardiac surgery. J. Am. Soc. Nephrol. 2018, 29, 670–679. [Google Scholar] [CrossRef]
- Nagler, A.; Firman, N.; Feferman, R.; Cotev, S.; Pines, M.; Shoshan, S. Reduction in pulmonary fibrosis in vivo by halofuginone. Am. J. Respir. Crit. Care Med. 1996, 154, 1082–1086. [Google Scholar] [CrossRef]
- Bruck, R.; Genina, O.; Aeed, H.; Alexiev, R.; Nagler, A.; Avni, Y.; Pines, M. Halofuginone to prevent and treat thioacetamide-induced liver fibrosis in rats. Hepatology 2001, 33, 379–386. [Google Scholar] [CrossRef] [Green Version]
- Pines, M.; Knopov, V.; Genina, O.; Lavelin, I.; Nagler, A. Halofuginone, a specific inhibitor of collagen type i synthesis, prevents dimethylnitrosamine-induced liver cirrhosis. J. Hepatol. 1997, 27, 391–398. [Google Scholar] [CrossRef]
- Li, J.; Qu, X.; Yao, J.; Caruana, G.; Ricardo, S.D.; Yamamoto, Y.; Yamamoto, H.; Bertram, J.F. Blockade of endothelial-mesenchymal transition by a smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy. Diabetes 2010, 59, 2612–2624. [Google Scholar] [CrossRef] [Green Version]
- Nakao, A.; Fujii, M.; Matsumura, R.; Kumano, K.; Saito, Y.; Miyazono, K.; Iwamoto, I. Transient gene transfer and expression of smad7 prevents bleomycin-induced lung fibrosis in mice. J. Clin. Investig. 1999, 104, 5–11. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Terada, Y.; Hanada, S.; Nakao, A.; Kuwahara, M.; Sasaki, S.; Marumo, F. Gene transfer of smad7 using electroporation of adenovirus prevents renal fibrosis in post-obstructed kidney. Kidney Int. 2002, 61, S94–S98. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Haidar, Z.S.; Hamdy, R.C.; Tabrizian, M. Delivery of recombinant bone morphogenetic proteins for bone regeneration and repair. Part a: Current challenges in bmp delivery. Biotechnol. Lett. 2009, 31, 1817–1824. [Google Scholar] [CrossRef] [PubMed]
- Swencki-Underwood, B.; Mills, J.K.; Vennarini, J.; Boakye, K.; Luo, J.; Pomerantz, S.; Cunningham, M.R.; Farrell, F.X.; Naso, M.F.; Amegadzie, B. Expression and characterization of a human bmp-7 variant with improved biochemical properties. Protein Expr. Purif. 2008, 57, 312–319. [Google Scholar] [CrossRef] [PubMed]
- Coffey, R.J., Jr.; Kost, L.J.; Lyons, R.M.; Moses, H.L.; LaRusso, N.F. Hepatic processing of transforming growth factor beta in the rat. Uptake, metabolism, and biliary excretion. J. Clin. Investig. 1987, 80, 750–757. [Google Scholar] [CrossRef] [Green Version]
- Kowalczewski, C.J.; Saul, J.M. Biomaterials for the delivery of growth factors and other therapeutic agents in tissue engineering approaches to bone regeneration. Front. Pharm. 2018, 9, 513. [Google Scholar] [CrossRef] [Green Version]
- Heinonen, A.M.; Rahman, M.; Dogbevia, G.; Jakobi, H.; Wölfl, S.; Sprengel, R.; Schwaninger, M. Neuroprotection by raav-mediated gene transfer of bone morphogenic protein 7. BMC Neurosci. 2014, 15, 38. [Google Scholar] [CrossRef] [Green Version]
- Lee, L.R.; Peacock, L.; Lisowski, L.; Little, D.G.; Munns, C.F.; Schindeler, A. Targeting adeno-associated virus vectors for local delivery to fractures and systemic delivery to the skeleton. Mol. Methods Clin. Dev. 2019, 15, 101–111. [Google Scholar] [CrossRef] [Green Version]
- Guggino, W.B.; Cebotaru, L. Adeno-associated virus (aav) gene therapy for cystic fibrosis: Current barriers and recent developments. Expert Opin. Biol. 2017, 17, 1265–1273. [Google Scholar] [CrossRef]
- Kim, N.H.; Cha, Y.H.; Kim, H.S.; Lee, S.E.; Huh, J.K.; Kim, J.K.; Kim, J.M.; Ryu, J.K.; Kim, H.J.; Lee, Y.; et al. A platform technique for growth factor delivery with novel mode of action. Biomaterials 2014, 35, 9888–9896. [Google Scholar] [CrossRef]
- Kim, S.; Shin, D.H.; Nam, B.Y.; Kang, H.-Y.; Park, J.; Wu, M.; Kim, N.H.; Kim, H.S.; Park, J.T.; Han, S.H.; et al. Newly designed protein transduction domain (ptd)-mediated bmp-7 is a potential therapeutic for peritoneal fibrosis. J. Cell. Mol. Med. 2020. [Google Scholar] [CrossRef] [PubMed]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Zhang, X.; Yun, J.S.; Han, D.; Yook, J.I.; Kim, H.S.; Cho, E.S. TGF-β Pathway in Salivary Gland Fibrosis. Int. J. Mol. Sci. 2020, 21, 9138. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239138
Zhang X, Yun JS, Han D, Yook JI, Kim HS, Cho ES. TGF-β Pathway in Salivary Gland Fibrosis. International Journal of Molecular Sciences. 2020; 21(23):9138. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239138
Chicago/Turabian StyleZhang, Xianglan, Jun Seop Yun, Dawool Han, Jong In Yook, Hyun Sil Kim, and Eunae Sandra Cho. 2020. "TGF-β Pathway in Salivary Gland Fibrosis" International Journal of Molecular Sciences 21, no. 23: 9138. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239138