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Special Issue "Recent Advances in Salivary Gland and Their Function"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 May 2021).

Special Issue Editor

Prof. Dr. Sang-Gun Ahn
E-Mail
Guest Editor
Department of Pathology, School of Dentistry, Chosun University 309 Pilmun-daero, Dong-gu, Gwangju, 61452, Korea
Interests: cellular stress defense mechanism; aging and metabolism; photodynamic therapy in cancer

Special Issue Information

Dear Colleagues,

Salivary gland dysfunctional changes occur with reduced salivary flow and dry mouth (xerostomia) and commonly involve oral dysfunction, tooth structure deterioration, and infection through reduced salivation. Anatomically, aging induces atrophy of acinar cells (ACs) and replacement of normal gland parenchyma with adipose tissue, connective tissue, and oncocytes. Recently, numerous medical drugs and treatments (radiation, chemotherapy) have been shown to significantly contribute to salivary gland dysfunction. Although changes associated with salivary gland dysfunction are affected by multiple factors, such as the environment, not all changes are considered to be physiological, and how aging influences the function of salivary glands is unclear.

This Special Issue discusses the mechanism of aging–salivary gland disorder, and new entities, such as functional regeneration of the salivary gland. Furthermore, we provide an overview of new advances in the diagnostic, prognostic, and therapeutic implications of aging and the salivary gland.

Prof. Sang-Gun Ahn
Guest Editor

Manuscript Submission Information

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Keywords

  • Salivary gland
  • Aging
  • Oral dysfunction
  • Functional regeneration
  • Metabolism

Published Papers (7 papers)

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Research

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Article
Differential Expression of Peroxisomal Proteins in Distinct Types of Parotid Gland Tumors
Int. J. Mol. Sci. 2021, 22(15), 7872; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22157872 - 23 Jul 2021
Viewed by 139
Abstract
Salivary gland cancers are rare but aggressive tumors that have poor prognosis and lack effective cure. Of those, parotid tumors constitute the majority. Functioning as metabolic machinery contributing to cellular redox balance, peroxisomes have emerged as crucial players in tumorigenesis. Studies on murine [...] Read more.
Salivary gland cancers are rare but aggressive tumors that have poor prognosis and lack effective cure. Of those, parotid tumors constitute the majority. Functioning as metabolic machinery contributing to cellular redox balance, peroxisomes have emerged as crucial players in tumorigenesis. Studies on murine and human cells have examined the role of peroxisomes in carcinogenesis with conflicting results. These studies either examined the consequences of altered peroxisomal proliferators or compared their expression in healthy and neoplastic tissues. None, however, examined such differences exclusively in human parotid tissue or extended comparison to peroxisomal proteins and their associated gene expressions. Therefore, we examined differences in peroxisomal dynamics in parotid tumors of different morphologies. Using immunofluorescence and quantitative PCR, we compared the expression levels of key peroxisomal enzymes and proliferators in healthy and neoplastic parotid tissue samples. Three parotid tumor subtypes were examined: pleomorphic adenoma, mucoepidermoid carcinoma and acinic cell carcinoma. We observed higher expression of peroxisomal matrix proteins in neoplastic samples with exceptional down regulation of certain enzymes; however, the degree of expression varied between tumor subtypes. Our findings confirm previous experimental results on other organ tissues and suggest peroxisomes as possible therapeutic targets or markers in all or certain subtypes of parotid neoplasms. Full article
(This article belongs to the Special Issue Recent Advances in Salivary Gland and Their Function)
Article
Muscarinic Receptors and BK Channels Are Affected by Lipid Raft Disruption of Salivary Gland Cells
Int. J. Mol. Sci. 2021, 22(9), 4780; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094780 - 30 Apr 2021
Viewed by 377
Abstract
Activity-dependent fluid secretion is the most important physiological function of salivary glands and is regulated via muscarinic receptor signaling. Lipid rafts are important for G-protein coupled receptor (GPCR) signaling and ion channels in plasma membranes. However, it is not well understood whether lipid [...] Read more.
Activity-dependent fluid secretion is the most important physiological function of salivary glands and is regulated via muscarinic receptor signaling. Lipid rafts are important for G-protein coupled receptor (GPCR) signaling and ion channels in plasma membranes. However, it is not well understood whether lipid raft disruption affects all membrane events or only specific functions in muscarinic receptor-mediated water secretion in salivary gland cells. We investigated the effects of lipid raft disruption on the major membrane events of muscarinic transcellular water movement in human salivary gland (HSG) cells. We found that incubation with methyl-β-cyclodextrin (MβCD), which depletes lipid rafts, inhibited muscarinic receptor-mediated Ca2+ signaling in HSG cells and isolated mouse submandibular acinar cells. However, MβCD did not inhibit a Ca2+ increase induced by thapsigargin, which activates store-operated Ca2+ entry (SOCE). Interestingly, MβCD increased the activity of the large-conductance Ca2+-activated K+ channel (BK channel). Finally, we found that MβCD did not directly affect the translocation of aquaporin-5 (AQP5) into the plasma membrane. Our results suggest that lipid rafts maintain muscarinic Ca2+ signaling at the receptor level without directly affecting the activation of SOCE induced by intracellular Ca2+ pool depletion or the translocation of AQP5 into the plasma membrane. Full article
(This article belongs to the Special Issue Recent Advances in Salivary Gland and Their Function)
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Article
Epigallocatechin-3-Gallate Protects Pro-Acinar Epithelia Against Salivary Gland Radiation Injury
Int. J. Mol. Sci. 2021, 22(6), 3162; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063162 - 19 Mar 2021
Cited by 1 | Viewed by 722
Abstract
Antioxidant agents are promising pharmaceuticals to prevent salivary gland (SG) epithelial injury from radiotherapy and their associated irreversible dry mouth symptoms. Epigallocatechin-3-gallate (EGCG) is a well-known antioxidant that can exert growth or inhibitory biological effects in normal or pathological tissues leading to disease [...] Read more.
Antioxidant agents are promising pharmaceuticals to prevent salivary gland (SG) epithelial injury from radiotherapy and their associated irreversible dry mouth symptoms. Epigallocatechin-3-gallate (EGCG) is a well-known antioxidant that can exert growth or inhibitory biological effects in normal or pathological tissues leading to disease prevention. The effects of EGCG in the various SG epithelial compartments are poorly understood during homeostasis and upon radiation (IR) injury. This study aims to: (1) determine whether EGCG can support epithelial proliferation during homeostasis; and (2) investigate what epithelial cells are protected by EGCG from IR injury. Ex vivo mouse SG were treated with EGCG from 7.5–30 µg/mL for up to 72 h. Next, SG epithelial branching morphogenesis was evaluated by bright-field microscopy, immunofluorescence, and gene expression arrays. To establish IR injury models, linear accelerator (LINAC) technologies were utilized, and radiation doses optimized. EGCG epithelial effects in these injury models were assessed using light, confocal and electron microscopy, the Griess assay, immunohistochemistry, and gene arrays. SG pretreated with EGCG 7.5 µg/mL promoted epithelial proliferation and the development of pro-acinar buds and ducts in regular homeostasis. Furthermore, EGCG increased the populations of epithelial progenitors in buds and ducts and pro-acinar cells, most probably due to its observed antioxidant activity after IR injury, which prevented epithelial apoptosis. Future studies will assess the potential for nanocarriers to increase the oral bioavailability of EGCG. Full article
(This article belongs to the Special Issue Recent Advances in Salivary Gland and Their Function)
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Article
Choline Acetyltransferase Induces the Functional Regeneration of the Salivary Gland in Aging SAMP1/Kl -/- Mice
Int. J. Mol. Sci. 2021, 22(1), 404; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010404 - 02 Jan 2021
Cited by 1 | Viewed by 653
Abstract
Salivary gland dysfunction induces salivary flow reduction and a dry mouth, and commonly involves oral dysfunction, tooth structure deterioration, and infection through reduced salivation. This study aimed to investigate the impact of aging on the salivary gland by a metabolomics approach in an [...] Read more.
Salivary gland dysfunction induces salivary flow reduction and a dry mouth, and commonly involves oral dysfunction, tooth structure deterioration, and infection through reduced salivation. This study aimed to investigate the impact of aging on the salivary gland by a metabolomics approach in an extensive aging mouse model, SAMP1/Klotho -/- mice. We found that the salivary secretion of SAMP1/Klotho -/- mice was dramatically decreased compared with that of SAMP1/Klotho WT (+/+) mice. Metabolomics profiling analysis showed that the level of acetylcholine was significantly decreased in SAMP1/Klotho -/- mice, although the corresponding levels of acetylcholine precursors, acetyl-CoA and choline, increased. Interestingly, the mRNA and protein expression of choline acetyltransferase (ChAT), which is responsible for catalyzing acetylcholine synthesis, was significantly decreased in SAMP1/Klotho -/- mice. The overexpression of ChAT induced the expression of salivary gland functional markers (α–amylase, ZO-1, and Aqua5) in primary cultured salivary gland cells from SAMP1/Klotho +/+ and -/- mice. In an in vivo study, adeno-associated virus (AAV)-ChAT transduction significantly increased saliva secretion compared with the control in SAMP1/Klotho -/- mice. These results suggest that the dysfunction in acetylcholine biosynthesis induced by ChAT reduction may cause impaired salivary gland function Full article
(This article belongs to the Special Issue Recent Advances in Salivary Gland and Their Function)
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Review

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Review
2021 Update on Diagnostic Markers and Translocation in Salivary Gland Tumors
Int. J. Mol. Sci. 2021, 22(13), 6771; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136771 - 24 Jun 2021
Viewed by 448
Abstract
Salivary gland tumors are a rare tumor entity within malignant tumors of all tissues. The most common are malignant mucoepidermoid carcinoma, adenoid cystic carcinoma, and acinic cell carcinoma. Pleomorphic adenoma is the most recurrent form of benign salivary gland tumor. Due to their [...] Read more.
Salivary gland tumors are a rare tumor entity within malignant tumors of all tissues. The most common are malignant mucoepidermoid carcinoma, adenoid cystic carcinoma, and acinic cell carcinoma. Pleomorphic adenoma is the most recurrent form of benign salivary gland tumor. Due to their low incidence rates and complex histological patterns, they are difficult to diagnose accurately. Malignant tumors of the salivary glands are challenging in terms of differentiation because of their variability in histochemistry and translocations. Therefore, the primary goal of the study was to review the current literature to identify the recent developments in histochemical diagnostics and translocations for differentiating salivary gland tumors. Full article
(This article belongs to the Special Issue Recent Advances in Salivary Gland and Their Function)
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Review
Aging-Related Metabolic Dysfunction in the Salivary Gland: A Review of the Literature
Int. J. Mol. Sci. 2021, 22(11), 5835; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115835 - 29 May 2021
Viewed by 634
Abstract
Aging-related salivary dysfunction commonly induces the poor oral health, including decreased saliva flow and dental caries. Although the clinical significance of the salivary glands is well-known, the complex metabolic pathways contributing to the aging-dysfunction process are only beginning to be uncovered. Here, we [...] Read more.
Aging-related salivary dysfunction commonly induces the poor oral health, including decreased saliva flow and dental caries. Although the clinical significance of the salivary glands is well-known, the complex metabolic pathways contributing to the aging-dysfunction process are only beginning to be uncovered. Here, we provide a comprehensive overview of the metabolic changes in aging-mediated salivary gland dysfunction as a key aspect of oral physiology. Several metabolic neuropeptides or hormones are involved in causing or contributing to salivary gland dysfunction, including hyposalivation and age-related diseases. Thus, aging-related metabolism holds promise for early diagnosis, increased choice of therapy and the identification of new metabolic pathways that could potentially be targeted in salivary gland dysfunction. Full article
(This article belongs to the Special Issue Recent Advances in Salivary Gland and Their Function)
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Review
TGF-β Pathway in Salivary Gland Fibrosis
Int. J. Mol. Sci. 2020, 21(23), 9138; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239138 - 30 Nov 2020
Cited by 1 | Viewed by 720
Abstract
Fibrosis is presented in various physiologic and pathologic conditions of the salivary gland. Transforming growth factor beta (TGF-β) pathway has a pivotal role in the pathogenesis of fibrosis in several organs, including the salivary glands. Among the TGF-β superfamily members, TGF-β1 and 2 [...] Read more.
Fibrosis is presented in various physiologic and pathologic conditions of the salivary gland. Transforming growth factor beta (TGF-β) pathway has a pivotal role in the pathogenesis of fibrosis in several organs, including the salivary glands. Among the TGF-β superfamily members, TGF-β1 and 2 are pro-fibrotic ligands, whereas TGF-β3 and some bone morphogenetic proteins (BMPs) are anti-fibrotic ligands. TGF-β1 is thought to be associated with the pro-fibrotic pathogenesis of sialadenitis, post-radiation salivary gland dysfunction, and Sjögren’s syndrome. Potential therapeutic strategies that target multiple levels in the TGF-β pathway are under preclinical and clinical research for fibrosis. Despite the anti-fibrotic effect of BMPs, their in vivo delivery poses a challenge in terms of adequate clinical efficacy. In this article, we will review the relevance of TGF-β signaling in salivary gland fibrosis and advances of potential therapeutic options in the field. Full article
(This article belongs to the Special Issue Recent Advances in Salivary Gland and Their Function)
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