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人工合成小分子多肽P16抑制大鼠肾小管上皮细胞纤维化的初步研究
引用本文:王巍,石毓君,张立,李青,涂智丹,叶丰,王进京,步宏. 人工合成小分子多肽P16抑制大鼠肾小管上皮细胞纤维化的初步研究[J]. 四川大学学报(医学版), 2007, 38(4): 590-594
作者姓名:王巍  石毓君  张立  李青  涂智丹  叶丰  王进京  步宏
作者单位:四川大学华西医院,移植免疫试验室,成都,610041;四川大学华西医院,移植免疫试验室,成都,610041;四川大学华西医院,移植免疫试验室,成都,610041;四川大学华西医院,移植免疫试验室,成都,610041;四川大学华西医院,移植免疫试验室,成都,610041;四川大学华西医院,移植免疫试验室,成都,610041;四川大学华西医院,移植免疫试验室,成都,610041;四川大学华西医院,移植免疫试验室,成都,610041
基金项目:国家重点基础研究发展计划(973计划) , 国家自然科学基金 , 美国中华医学会基金
摘    要:目的 观察人工合成的与结缔组织生长因子(CTGF)同源的16个氨基酸小分子多肽(P16)能否与CTGF竞争性地和CTGF受体相结合,以阻止大鼠肾小管上皮细胞(NRK-52E)转分化为肌纤维母细胞,并抑制细胞纤维化的发生.方法 以NRK-52E细胞株为实验对象,用异硫氰酸荧光素标记P16(FITC-P16),激光共聚焦显微镜观察P16和CTGF与细胞竞争性结合能力.用CTGF诱导NRK-52E细胞并加入P16竞争结合,通过细胞免疫荧光和RT-PCR分别在蛋白和基因水平上检测反映NRK-52E细胞向肌纤维母细胞转化的α-平滑肌肌动蛋白(α-smooth action muscle protein, α-SMA)和反映NRK-52E细胞纤维化的胶原Ⅰ和Ⅳ.结果 CTGF能诱导NRK-52E细胞高表达α-SMA和胶原Ⅰ、Ⅳ.P16可与CTGF竞争性结合细胞表面的整合素аvβ3,并显著抑制CTGF诱导的α-SMA和胶原Ⅰ、Ⅳ高表达.结论 人工合成的小分子多肽P16可通过与CTGF竞争性结合于细胞表面,显著抑制CTGF的促细胞转分化和纤维化作用,可望成为抗纤维化治疗的一种新策略.

关 键 词:P16  CTGF  转分化  纤维化
修稿时间:2006-11-022007-03-06

Effect of Synthesized Polypeptide (P16) on Inhibiting Cell Transdifferentiation and Fibrosis Induced by Connective Tissue Growth Factor
WANG Wei,SHI Yu-jun,ZHANG Li,LI Qing,QIU Jing,TU Zhi-dan,YE Feng,BU Hong. Effect of Synthesized Polypeptide (P16) on Inhibiting Cell Transdifferentiation and Fibrosis Induced by Connective Tissue Growth Factor[J]. Journal of Sichuan University. Medical science edition, 2007, 38(4): 590-594
Authors:WANG Wei  SHI Yu-jun  ZHANG Li  LI Qing  QIU Jing  TU Zhi-dan  YE Feng  BU Hong
Affiliation:Key Laboratory of Transplant Engineering and Immunology, Ministry Of Health, West China Hospital, Sichuan University, Chengdu 610041, China
Abstract:OBJECTIVE: To explore the possibility of a CTGF originated hexadeca-peptide (named P16) to compete with the CTGF in binding integrin avP3 on rat tubular epithelial cells (NRK-52E) and inhibit the transdifferentiation and myofibroblasts of NRK-52E cells induced by CTGF. METHODS: The NRK-52E cells were cultured in a condition with the existence of CTGF, P16-FITC (P16 labeled with fluorescein isothiocyanate), or both for 24h. The immunofluorescence staining and RT-PCR were employed to detect the expressions of the protein and mRNA of alpha-SMA and the collagen I and IV which indicate the cell trans-differentiation and fibrosis. RESULTS: The P16 had stronger affinity with the NRK-52E cells than the CTGF. In a CTGF and P16 co-culture system, the P16 inhibited the expression of a-SMA, collagen I and IV up-regulated by the CTGF. However, P16 alone had no effect on cell trans-differentiation and fibrosis. CONCLUSION: The synthesized P16 is capable of binding with NRK-52E cells and inhibiting trans-differentiation and fibrosis of the NRK-52E cells induced by CTGF in vitro. This finding offers a possibility of developing a novel antifibrosis therapy that targets CTGF receptor.
Keywords:P16 CTGF Trans-differentiation Fibrosis
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