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Article

Tauroursodeoxycholic Acid Decreases Keloid Formation by Reducing Endoplasmic Reticulum Stress as Implicated in the Pathogenesis of Keloid

1
Department of Plastic and Reconstructive Surgery, College of Medicine, Chungnam National University, Daejeon 35015, Korea
2
Research Institute for Medicinal Sciences, College of Medicine, Chungnam National University, Daejeon 35015, Korea
3
Center for Research Equipment, Korea Basic Science Institute, Daejeon 34133, Korea
4
Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea
5
Department of Physiology, College of Medicine, Chungnam National University, Daejeon 35015, Korea
6
Department of Pathology, College of Medicine, Chungnam National University, Daejeon 35015, Korea
7
Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 35015, Korea
8
Brain Research Institute, College of Medicine, Chungnam National University, Daejeon 35015, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Anagha Malur and Michael Roth
Int. J. Mol. Sci. 2021, 22(19), 10765; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910765
Received: 20 August 2021 / Revised: 1 October 2021 / Accepted: 3 October 2021 / Published: 5 October 2021
Keloids are a common form of pathologic wound healing and are characterized by an excessive production of extracellular matrix. This study examined the major contributing mechanism of human keloid pathogenesis using transcriptomic analysis. We identified the upregulation of mitochondrial oxidative stress response, protein processing in the endoplasmic reticulum, and TGF-β signaling in human keloid tissue samples compared to controls, based on ingenuity pathway and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Electron microscopic examinations revealed an increased number of dysmorphic mitochondria and expanded endoplasmic reticulum (ER) in human keloid tissue samples than that in controls. Western blot analysis performed using human tissues suggested noticeably higher ER stress signaling in keloids than in normal tissues. Treatment with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, significantly decreased scar formation in rabbit models, compared to normal saline and steroid injections. In summary, our findings demonstrate the contributions of mitochondrial dysfunction and dysregulated ER stress signaling in human keloid formation and the potential of TUDCA in the treatment of keloids. View Full-Text
Keywords: tauroursodeoxycholic acid; TUDCA; endoplasmic reticulum stress; ER stress; mitochondria; keloid tauroursodeoxycholic acid; TUDCA; endoplasmic reticulum stress; ER stress; mitochondria; keloid
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MDPI and ACS Style

Kim, S.; Lee, S.E.; Yi, S.; Jun, S.; Yi, Y.-S.; Nagar, H.; Kim, C.-S.; Shin, C.; Yeo, M.-K.; Kang, Y.E.; Oh, S.-H. Tauroursodeoxycholic Acid Decreases Keloid Formation by Reducing Endoplasmic Reticulum Stress as Implicated in the Pathogenesis of Keloid. Int. J. Mol. Sci. 2021, 22, 10765. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910765

AMA Style

Kim S, Lee SE, Yi S, Jun S, Yi Y-S, Nagar H, Kim C-S, Shin C, Yeo M-K, Kang YE, Oh S-H. Tauroursodeoxycholic Acid Decreases Keloid Formation by Reducing Endoplasmic Reticulum Stress as Implicated in the Pathogenesis of Keloid. International Journal of Molecular Sciences. 2021; 22(19):10765. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910765

Chicago/Turabian Style

Kim, Sunje, Seong E. Lee, Shinae Yi, Sangmi Jun, Yoon-Sun Yi, Harsha Nagar, Cuk-Seong Kim, Chungmin Shin, Min-Kyung Yeo, Yea E. Kang, and Sang-Ha Oh. 2021. "Tauroursodeoxycholic Acid Decreases Keloid Formation by Reducing Endoplasmic Reticulum Stress as Implicated in the Pathogenesis of Keloid" International Journal of Molecular Sciences 22, no. 19: 10765. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910765

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