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系統識別號 U0026-0812200915281391
論文名稱(中文) TLE2和Hes6在肌肉分化中所扮演的角色
論文名稱(英文) The role of TLE2 and Hes6 in muscle differentiation
校院名稱 成功大學
系所名稱(中) 藥理學研究所
系所名稱(英) Department of Pharmacology
學年度 97
學期 2
出版年 98
研究生(中文) 李美璇
研究生(英文) Mei-Hsuang Lee
電子信箱 s2695408@mail.ncku.edu.tw
學號 s2695408
學位類別 碩士
語文別 中文
論文頁數 61頁
口試委員 口試委員-吳昭良
口試委員-劉校生
口試委員-馬明琪
指導教授-呂增宏
中文關鍵字 肌肉分化 
英文關鍵字 Hes6  TLE2 
學科別分類
中文摘要 近年來,肌肉幹細胞 (muscle stem cell) 的發現,使我們瞭解到肌肉分化除了發生在胚胎時期,也會發生在成人的身上,例如:運動或是受傷時,位於肌肉basal lamina下方的衛星細胞 (satellite cell) 為了因應身體的需求,會被活化、增生,並且分化成肌纖維母細胞,再進一步分化成有功能的肌肉,補充身體的需求。然而,對於衛星細胞如何受到外界刺激調控,仍然有許多未知之處。目前已知,會促進肌肉分化的基因除了MyoD、Myogenin等MRFs (muscle regulatory transcription factors)以外,也有越來越多研究指出,Hes6 (hairy enhancer of split 6)也參與在神經、肌肉的發育過程當中,並且其WRPW motif被認為扮演著重要的角色。其中,會藉由WRPW motif和Hes family結合的蛋白質已知為TLE family,並且也有許多研究指出,TLE family參與許多發育的調控。因此本篇研究即探討TLE2是否參與在Hes6蛋白對於肌肉分化的調控當中。結果發現,大量表達TLE2蛋白質會抑制C2C12細胞的myogenin mRNA轉錄,以及抑制肌肉管的形成,其中機制是透過抑制Hes6蛋白質表現;另外一方面,大量表達Hes6蛋白質也會促進TLE2蛋白分解,使TLE2 過量表現的細胞能夠分化。這些結果顯示,TLE2抑制Hes6所調控的肌肉分化,使不分化的細胞增加,可能參與肌肉幹細胞保存的過程。
英文摘要 The discovery of muscle stem cell leads us to understand that muscle differentiation not only occur in embryonic stage but also in adult. For example, in exercise or injuries, satellite cell located under basal lamina will be activated, proliferate, and differentiate into myoblasts. Then, myoblasts fuse into myotubes to supply the needs of body. More and more researches indicate that Hes6 transcription factor participates in the regulation of neurogenesis and myogenesis, and its WRPW motif is essential for muscle differentiation. On the other hand, TLE family proteins, which may participate in the regulation of many developmental processes, interact with Hes family protein through the WRPW motif of Hes. We are interested to study how TLE2 regulate muscle differentiation via Hes6. We found TLE2 was increased along myotubes formation from C2C12 cells. And overexpressing TLE2 or TLE1 inhibited myogenin expression and myotubes formation accompanying with down-regulation of Hes6. On the other hand, forced expression of Hes6 in TLE2 overexpressing C2C12 cells facilitates TLE2 protein degradation and restores the ability of TLE2 overexpressing cells to differentiate. Our results indicate that TLE family proteins are inhibitors of muscle differentiation and negatively regulate myotube formation, which might be required for myogenic cells to remain in an undifferentiated stage for next muscle regulation.
論文目次 縮寫檢索表01
緒論03
實驗材料與方法17
實驗結果33
討論39
圖表44
參考文獻52
附錄57
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