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

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。

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（P0.01）.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.