肝细胞生长因子和血管紧张素Ⅱ对肾小管上皮细胞转分化的影响及其作用机制

目的: 探讨肝细胞生长因子(HGF)和血管紧张素Ⅱ(AngⅡ)对肾小管上皮-肌成纤维细胞转分化(TEMT)的影响,并阐明其作用机制。方法: 体外培养人近曲小管上皮HK-2细胞,取Ⅳ期细胞分为对照组、AngⅡ(1×10^-6mol·L^-1)组、HGF(8 μg·L^-1)组和AngⅡ(1×10^-6mol·L^-1)+HGF(8 μg·L^-1)组。采用CCK8法检测HK-2细胞增殖情况,RT-PCR法检测α-平滑肌肌动蛋白(α-SMA)mRNA表达水平,Western blotting法检测α-SMA的蛋白表达水平。结果: 与对照组比较,AngⅡ组HK-2细胞增殖活性降低(P<0.01),HGF组HK-2细胞增殖活性升高(P<0.05),AngⅡ+HGF组HK-2细胞增殖活性降低(P<0.05)。与对照组比较,AngⅡ组 HK-2细胞中α-SMA mRNA及蛋白表达水平升高(P<0.05或P<0.01),HGF组HK-2细胞中α-SMA mRNA及蛋白表达水平降低(P<0.05或P<0.01), AngⅡ+HGF组HK-2细胞α-SMA mRNA及蛋白表达水平降低(P<0.05); 与AngⅡ 组比较,AngⅡ+HGF组细胞增殖活性升高(P<0.05),α-SMA mRNA及蛋白表达水平降低(P<0.05)。结论: AngⅡ抑制肾小管上皮细胞增生而促进TEMT, HGF促进肾小管上皮细胞增生而抑制TEMT,HGF可能介导AngⅡ抑制HK-2细胞增生及促进TEMT的作用。

Effects of hepatocyte growth factor and angiotensin Ⅱ on transdifferentiation of tubular epithelial-myofibroblasts and their mechanisms

Objective To explore the effects of hepatocyte growth factor (HGF) and angiotensin Ⅱ (Ang Ⅱ) on the tubular epithelial myofibroblasts (TEMT) transdifferentiation,and to clarify their mechanisms. Methods The cultured human proximal convoluted tubule HK-2 cells in vitro at stage Ⅳ were divided into control group,AngⅡ(1×10^-6mol·L^-1) group,HGF(8 μg·L^-1)group,AngⅡ(1×10^-6mol·L^-1)+HGF(8 μg·L^-1)group.The proliferation of HK-2 cells was detected by CCK8 method;the expressions of α-smooth muscle actin (α-SMA) mRNA were detected by RT-PCR and the α-SMA protein expression levels were detected by Western blotting method. Results Compared with control group,the proliferation activity of cells in AngⅡ group was decreased (P<0.01),the proliferation activity of the HK-2 cells in HGF group was increased(P<0.05),and it was also decreased in AngⅡ+HGF group (P<0.05).Compared with control group,the α-SMA mRNA and protein expression levels in the HK-2 cells in AngⅡ group were increased (P<0.05 or P<0.01), and the expression levels of α-SMA mRNA and protein in HGF group were decreased (P<0.05 or P<0.01).Compared with AngⅡ group,the proliferation activity of HK-2 cells were increased (P<0.05),and the α-SMA mRNA and protein expression levels in AngⅡ+HGF group were decreased (P<0.05). Conclusion AngⅡ can inhabit the proliferation of HK-2 cells and promote TEMT.HGF can promote the proliferation of HK-2 cells and inhabit TEMT.HGF may interfere the effects of AngⅡ on inhibiting the proliferation of HK-2 cells and promoting TEMT.