Downregulation of histone deacetylase 8 (HDAC8) alleviated the progression of oral submucous fibrosis

Hui Wen Yang, Yi Hwa Sun, Chih Yuan Fang, Yoichi Ohiro, Heng Yi Liao, Yi Wen Liao, Yu Hsun Kao, Cheng Chia Yu

研究成果: 雜誌貢獻文章同行評審

4 引文 斯高帕斯(Scopus)

摘要

Background/purpose: Oral submucous fibrosis (OSF) is a premalignant disorder that is associated with betel nut chewing. The purpose of the study was to establish the role of histone deacetylase (HDAC) 8, one of histone deacetylases, in the regulation of fibrotic conditions to provide a therapeutic potential for OSF. Materials and methods: First, we examined the expression of HDAC8 in fibrotic buccal mucosal fibroblasts (fBMFs) and OSF tissues. Markers of myofibroblasts and TGF-β signaling were conducted in fBMFs with HDAC8 knockdown were examined. Furthermore, epithelial–mesenchymal transition (EMT) markers, collagen gel contraction and migration ability were also examined in fBMFs transfected with sh-HDAC8. HDAC8 inhibitor was used to analyze the collagen gel contraction and wound healing ability in fBMFs. Results: We observed the mRNA expression of HDAC8 was significantly increased in fBMFs. Compared to normal tissues, the protein level of HDAC8 was upregulated in OSF. Next, mRNA and protein expression of HDAC8 was significantly decreased, accompanying downregulation of α-SMA and COL1A1 in fBMFs infected with sh-HDAC8. To determine the critical role of HDAC8 in OSF fibrogenesis, results revealed that TGF-β secretion and the expression of EMT transcription factor SNAIL and p-Smad were significantly decreased in HDAC8-knockdown fBMFs. We further demonstrated that collagen gel contraction and migration ability were significantly decreased in fBMFs transfected with sh-HDAC8. Last, results revealed that significantly reduced collagen gel contraction and wound healing ability in fBMFs with HDAC8 inhibitor treatment. Conclusion: We concluded that downregulation of HDAC8 alleviated the activities of myofibroblasts and TGF-β/Smad signaling pathway in OSF.
原文英語
頁(從 - 到)652-658
頁數7
期刊Journal of Dental Sciences
18
發行號2
DOIs
出版狀態已發佈 - 4月 2023

ASJC Scopus subject areas

  • 一般牙醫學

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