Twist表現量和口腔黏膜下纖維化之關係探討

中山醫學大學機構典藏 CSMUIR > 口腔醫學院 > 口腔醫學研究所 > 博碩士論文 > Item 310902500/20221

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題名:	Twist表現量和口腔黏膜下纖維化之關係探討 The relationship between Twist expression and oral submucous fibrosis
作者:	李育賢 Lee, Yu-Hsien
貢獻者:	中山醫學大學口腔醫學研究所;黃裕峰
關鍵詞:	口腔黏膜下纖維化;檳榔素;肌纖維母細胞;Twist
日期:	2015-06
上傳時間:	2019-06-11T03:21:31Z (UTC)
摘要:	口腔黏膜下纖維化(oral submucous fibrosis, OSF)是一種慢性疤痕變化的疾病，被視為是口腔黏膜癌前病變。本實驗中，我們探討Twist-一種上皮細胞轉型成間質細胞(epithelial-mesenchymal transition, EMT)的轉錄因子，在口腔黏膜下纖維化中肌纖維母細胞(myofibroblastic)分化所佔有的功能性角色。在原代人類頰黏膜纖維母細胞培養中(primary buccal mucosal fibroblasts, BMFs)，加入檳榔素(arecoline)-檳榔鹼的主要成份，來研究Twist是否會和劑量呈相關性的表現。本實驗也探討經過檳榔素刺激的原代人類頰黏膜纖維母細胞及經過Twist knockdown的原代口腔黏膜下纖維化來源之纖維母細胞(primary oral submucous fibrosis-drived fibroblasts, OSFs)膠原蛋白凝膠收縮及細胞移動的能力是否有影響。我們發現Twist基因及蛋白質表現量與檳榔素劑量呈正相關。肌纖維母細胞的活動，包括膠原蛋白凝膠收縮及細胞移動的能力，也會因為檳榔素而增加；而當我們knockdown Twist的表現時，此現象也會跟著降低。重要的是在原代口腔黏膜下纖維化來源之纖維母細胞培養中， knockdown Twist也會抑制口腔黏膜下纖維化來源之纖維母細胞膠原蛋白凝膠收縮及細胞癒合的能力。臨床上，嚼食檳榔病人口腔黏膜下纖維化的組織相較於正常口腔黏膜的組織， Twist 在基因及蛋白質表現量都較高。這些證據顯示Twist的表現增加和嚼檳榔引起的口腔黏膜下纖維化可能有關，且會改變肌纖維母細胞的能力。 Oral submucous fibrosis (OSF), a chronic progressive scarring disease, has been considered as a pre-cancerous condition of oral mucosa. In the study, we investigated the functional role of Twist, an epithelial-mesenchymal transition (EMT) transcriptional factor, in myofibroblastic differentiation activity of OSF. Arecoline, a major areca nut alkaloid, was used to explore whether expression of Twist could be changed dose-dependently in human primary buccal mucosal fibroblasts (BMFs). Collagen gel contraction and migration capability in arecoline-stimulated BMFs and primary oral submucous fibrosis-derived fibroblasts (OSFs) with Twist knockdown was presented. We observed that the treatment of arecoline dose-dependently increased twist expression transcript and protein levels in BMFs. The myofibroblast activity including collagen gel contraction and migration capability also induced by arecoline, while knockdown of Twist reversed these phenomena. Importantly, inhibition of Twist led to the suppression collagen contraction and wound healing capability of primary cultivated OSFs. Clinically, Twist transcript and protein expression was higher expression in areca quid chewing-associated OSF tissues than in normal oral mucosa tissues. These evidences suggest that up-regulation of Twist might be involved in the pathogenesis of areca quid-associated OSF through dysregulation of myofibroblast activity.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/20221
顯示於類別:	[口腔醫學研究所] 博碩士論文

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