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蛋白酪氨酸磷酸酶SHP-2对AngⅡ刺激的心肌成纤维细胞增殖的影响

Role of protein tyrosine phosphatase SHP-2 in cardiac fibroblasts proliferation stimulated by Ang Ⅱ

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【作者】 张丽景金成艳王果元吴博李全凤徐长庆田野张力

【Author】 ZHANG Li-jing,JIN Cheng-yan,WANG Guo-yuan,WU Bo,LI Quan-feng,XU Chang-qing,TIAN Ye,ZHANG Li (Department of Pathophysiology,Harbin Medical University,Harbin 150081,China.)

【机构】 哈尔滨医科大学病理生理教研室

【摘要】 目的:探讨含有Src同源结构域2的蛋白酪氨酸磷酸酶2(Src homology 2 domain-containing pro-tein tyrosine phosphatase 2,SHP-2)对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)刺激的心肌成纤维细胞(cardiac fi-broblasts,CFs)增殖的作用。方法:差速贴壁法体外培养心肌成纤维细胞,以波形蛋白(vimentin)鉴定CFs纯度;MTT法检测AngⅡ作用下心肌成纤维细胞增殖率,采用重组腺病毒过表达SHP-2和SHP-2抑制剂NSC-87877分别对AngⅡ作用下的细胞增殖的影响。结果:AngⅡ对CFs增殖的促进作用有剂量依赖性,其促进细胞增殖的最高浓度为10-7mol/L;在AngⅡ的刺激下,SHP-2可以促进心肌成纤维细胞增殖,并且突变体组比野生型组增殖更明显(P<0.01)。SHP-2抑制剂NSC-87877达到50μmol/L时可以明显抑制AngⅡ刺激下的CFs增殖。结论:AngⅡ的促CFs增殖作用是通过SHP-2调控的。

【Abstract】 AIM: To investigate the potential role of Src homology 2 domain-containing protein tyrosine phosphatase 2(SHP-2) in the proliferation of cardiac fibroblasts induced by angiotensin Ⅱ(Ang Ⅱ).METHODS: The neonatal rat cardiac fibroblasts were separated by trypsin digestion.The cardiac fibroblasts were identified by vimentin of immunochemical staining.The proliferation of the cardiac fibroblasts with or without Ang Ⅱ stimulation was measured by MTT assay.Adenoviruses containing SHP-2 gene were transfected into cardiac fibroblasts to overexpress SHP-2.SHP-2 was inhibited by its inhibitor NSC-87877.RESULTS: The proliferation of the cardiac fibroblasts was increased in a dose-dependent manner by the stimulation of Ang Ⅱ and the maximum concentration of Ang II for cell proliferation was 10-7 mol/L.SHP-2 promoted the proliferation of cardiac fibroblasts under the stimulation of Ang Ⅱ.The proliferation rate in mutant group was higher than that in wild-type group(P<0.01).Inhibition of SHP-2 by NSC-87877 attenuated the proliferation.CONCLUSION: The growth promoting effect of Ang Ⅱ on cardiac fibroblasts is regulated by SHP-2.

【基金】 黑龙江省自然科学基金资助项目(No.D200842)
  • 【文献出处】 中国病理生理杂志 ,Chinese Journal of Pathophysiology , 编辑部邮箱 ,2012年02期
  • 【分类号】R363.1
  • 【被引频次】8
  • 【下载频次】191
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