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研究生： 古雁寧
Gu, Yan-Ning
論文名稱： 設計治療腎臟纖維化之抗乙型轉化生長因子及抗纖維黏蛋白雙特異性抗體
Design of Bispecific anti-TGF-β and Fibronectin EDA Antibody Targeting Renal Fibrosis
指導教授： 莊偉哲
Chuang, Woei-Jer
學位類別： 碩士
Master
系所名稱： 醫學院 - 生物化學暨分子生物學研究所
Department of Biochemistry and Molecular Biology
論文出版年： 2022
畢業學年度： 110
語文別： 英文
論文頁數： 48
中文關鍵詞： 纖維化 、慢性腎臟性疾病 、乙型轉化生長因子 、纖連蛋白 、細胞外基質 、整合素
外文關鍵詞： Fibrosis, Chronic kidney disease(CKD), TGF-β, ECM, Fibronectin, Integrin
相關次數： 點閱：111  下載：0 
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    • 摘要 I ABSTRACT III ACKNOWLEDGMENT IV CONTENTS VI LIST OF FIGURES VIII LIST OF TABLES IX ABBREVIATION X CHAPTER I INTRODUCTION 1 1.1 Renal fibrosis 1 1.2 Transforming growth factor-β: a master regulator of fibrogenesis 1 1.3 Fibronectin EDA (Fn-EDA) 2 1.4 Integrins 4 1.5 Current therapeutic strategies for renal fibrosis 5 CHAPTER II RATIONALE AND SPECIFIC AIMS 6 CHAPTER III MATERIAL AND METHODS 7 3.1 MATERIALS 7 3.1.1 Animals 7 3.1.2 Reagents and Kits 7 3.1.3 Buffers 7 3.1.5 Antibodies 10 3.2 METHODS 10 3.2.1 Protein expression in ExpiCHOTM expression system 11 3.2.2 Protein purification 11 3.2.3 In vivo assay 11 3.2.4 mRNA analysis 12 3.2.5 Histological analysis 14 3.2.6 Protein extraction 15 3.2.7 Western blotting 16 CHAPTER IV RESULTS 17 4.1 The expression and purification of recombinant bispecific anti-TGF-β antibodies 17 4.2 The animal model of renal fibrosis was successfully established and showed the increase fibronectin expression in fibrosis mice 17 4.3 The bispecific anti-TGF-β antibodies showed the better anti-fibrosis effect than anti-TGF-β 18 4.3.1 The mRNA analysis showed anti-fibrosis effect 18 4.3.2 The histological analysis showed anti-fibrosis effect 19 4.3.3 The protein quantification analysis showed anti-fibrosis effect 20 CHAPTER V DISCUSSION 21 5.1 The treatment time point of CKD to inhibit fibrogenesis 21 5.2 Fibronectin EDA may exhibit fibrosis activity independently 21 5.3 The therapeutic effect of α-TGF-β-KG is below expectations 22 CHAPTER VI CONCLUSIONS AND FUTURE PERSPECTIVE 24 REFERENCE 25 TABLES 29 FIGURES 30 APPENDIX FIGURES 38 APPENDIX TABLES 48

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