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

doi:10.13481/j.1671-587x.20150425

吉林大学学报(医学版) ›› 2015, Vol. 41 ›› Issue (04): 798-801.doi: 10.13481/j.1671-587x.20150425

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

王红月¹, 王茉¹, 张晨², 齐宏欣¹, 迟宝荣³

1. 吉林大学第一医院肾内科, 吉林长春 130021 ;
2. 吉林大学药学院再生医学系, 吉林长春 130021;
3. 吉林大学第一医院肝胆胰内科, 吉林长春 130021

收稿日期:2015-02-18 发布日期:2015-08-01
通讯作者: 迟宝荣,教授,博士研究生导师(Tel:0431-84808153,E-mail:why_changchun@sina.com) E-mail:why_changchun@sina.com
作者简介:王红月(1973-),女,吉林省长春市人,副主任医师,医学博士,主要从事肾病分子生物学方面的研究。
基金资助:
吉林省卫生厅科研基金资助课题(2009ZC041);吉林大学第一医院二部科研基金资助课题 (B007)

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

WANG Hongyue¹, WANG Mo¹, ZHANG Chen², QI Hongxin¹, CHI Baorong³

1. Department of Nephrology, First Hospital, Jilin University, Changchun 130021, China;
2. Department of Regenerative Medicine, School of Pharmacy, Jilin University, Changchun 130021, China;
3. Department of Gastroenterology, First Hospital, Jilin University, Changchun 130021, China

Received:2015-02-18 Published:2015-08-01

摘要/Abstract

摘要：

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。

关键词: 肝细胞生长因子, 肾小管上皮细胞, 转分化, 血管紧张素Ⅱ, &alpha, -平滑肌肌动蛋白

Abstract:

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.

Key words: hepatocyte growth factor, tubular epithelial myofibroblasts, transdifferentiation, angiotensin Ⅱ, α-smooth muscle actin

中图分类号:

Q813

王红月, 王茉, 张晨, 齐宏欣, 迟宝荣. 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[J]. 吉林大学学报(医学版), 2015, 41(04): 798-801.

WANG Hongyue, WANG Mo, ZHANG Chen, QI Hongxin, CHI Baorong. Effects of hepatocyte growth factor and angiotensin Ⅱ on transdifferentiation of tubular epithelial-myofibroblasts and their mechanisms[J]. Journal of Jilin University Medicine Edition, 2015, 41(04): 798-801.

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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

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

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