Ren Tingting, He Hongyan, Yu Xiaolan, Fan Junming, Tan Jian, Liu Jian
Department of Nephrology, Hospital Affiliated to Luzhou Medical College, Luzhou 646000, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2013 Jun;29(6):593-6.
To investigate the effect of angiotensin-(1-7) [Ang(1-7)] on the transdifferentiation of normal rat kidney proximal tubular epithelia cells (NRK52E) under hypoxic condition induced by cobaltous chloride (Co) and the underlying mechanism.
NRK52E cells were divided into control group, Co group, Co+Ang-(1-7) group and Ang-(1-7) group and cultured for 6 d. Expression levels of hypoxia-inducible factor-1α (HIF-lα) and α-smooth muscle actin (α-SMA) were detected by immunocytochemistry. Immunohistochemistry and Western blotting were used to determine the expression of p-ERK1/2 and ELISA to measure the content of collagen type 1 (Col I) in the culture supernatant.
Compared with the control group, the expressions of HIF-lα, α-SMA, Col Iand p-ERK1/2 in the Co group and the Co+Ang-(1-7) group increased significantly (P<0.05) 6 d later. Compared with the Co group, the expressions of HIF-lα, α-SMA, Col Iand p-ERK1/2 in the Co+Ang-(1-7) group decreased significantly (P<0.05).
Ang-(1-7) can inhibit Co-induced rats' tubular epithelial-to-mesenchymal transition and reduce the production of extracellular matrix. Inhibition of ERK1/2 pathway may play an important role in this process.
探讨血管紧张素-(1-7)[Ang(1-7)]对氯化钴(Co)诱导的低氧条件下正常大鼠肾近端小管上皮细胞(NRK52E)转分化的影响及其潜在机制。
将NRK52E细胞分为对照组、Co组、Co+Ang-(1-7)组和Ang-(1-7)组,培养6天。采用免疫细胞化学法检测缺氧诱导因子-1α(HIF-1α)和α-平滑肌肌动蛋白(α-SMA)的表达水平。采用免疫组织化学和蛋白质免疫印迹法检测p-ERK1/2的表达,采用酶联免疫吸附测定法检测培养上清液中Ⅰ型胶原(Col Ⅰ)的含量。
与对照组比较,6天后Co组和Co+Ang-(1-7)组HIF-1α、α-SMA、Col Ⅰ及p-ERK1/2表达均显著增加(P<0.05)。与Co组比较,Co+Ang-(1-7)组HIF-1α、α-SMA、Col Ⅰ及p-ERK1/2表达显著降低(P<0.05)。
Ang-(1-7)可抑制Co诱导的大鼠肾小管上皮-间充质转化,减少细胞外基质的产生。抑制ERK1/2通路可能在此过程中起重要作用。