• Shiuan-Chih Chen, Chia-Ming Liu, Pei-Ling Hsieh, Yi-Wen Liao, LinYi-Mei JoyYJInstitute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan., Cheng-Chia Yu, and Chuan-Hang Yu.
• Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
• J Formos Med Assoc. 2020 Feb 1; 119 (2): 595-600.

Background/PurposeOral submucous fibrosis (OSF) represents a precancerous lesion of oral mucosa that may progress into oral cancer and its major etiological factor is areca nut chewing. Carboxyl-terminus of Hsp70-interacting protein (CHIP) functions as an ubiquitin E3 ligase and is associated with fibrosis diseases. In the current study, we sought to investigate whether CHIP participated in the areca nut-mediated OSF development.MethodsThe mRNA expression of CHIP in arecoline-stimulated buccal mucosal fibroblasts (BMFs) and OSF tissues was determined by qRT-PCR. Collagen gel contraction, migration and invasion assays were carried out to evaluate the myofibroblast activation. The protein expression levels of α-SMA and transglutaminase 2 (TGM2) were assessed by Western blot.ResultsThe expression level of CHIP was reduced in BMFs following arecoline treatment in a dose-dependent manner, which was consistent with the observation of lower CHIP expression in OSF specimen compared to the normal counterparts. Ectopic expression of CHIP mitigated the myofibroblast activities, including elevated collagen gel contractility and cell motility. In addition, we showed that overexpression of CHIP downregulated the α-SMA and TGM-2 expression, which may lead to less fibrosis alteration.ConclusionCHIP may not only function as a key regulator of protein quality control but also a critical deciding factor to oral fibrogenesis. Our findings suggested that CHIP possesses the anti-fibrotic effect, which may be mediated by TGM2 regulation. Restoration of CHIP could be a therapeutic direction to help OSF patients.Copyright © 2019. Published by Elsevier B.V.

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