Kidney Protection against Ischemia/Reperfusion Injury by Myofibrillogenesis Regulator-1
Kidney Protection against Ischemia/Reperfusion Injury by Myofibrillogenesis Regulator-1
复制标题
肌原纤维生成调节因子 1 保护肾脏免受缺血/再灌注损伤
DOI：
10.1159/000360141
复制
发表时间：
2014-01-01
影响因子：
4.2
通讯作者：
Liu, Xiuhua
中科院分区：
文献类型：
--
作者：
Wang, Xiaoreng;Tao, Tianqi;Liu, Xiuhua
背景/目标：缺血/再灌注（I/R）损伤的特征在于近端小管上皮细胞的细胞骨架重组和极性丧失。以前，我们发现，肌原纤维生成调节因子（MR）-1促进心肌细胞中的肌动蛋白组织。方法：本研究观察了MR-1在I/R诱导的SD大鼠急性肾功能衰竭中的表达。我们测定了MR-1的表达和纤维肌动蛋白（F-actin）与球状肌动蛋白（G-actin）的比例。结果：缺氧/复氧（H/R）和缺氧/复氧（H/R）均可导致HK-2细胞MR-1、F-/G-actin比值和肌球蛋白轻链（MLC-2）的表达降低，MR-1表达增加或RNA干扰沉默。MR-1过表达减弱了H/R诱导的细胞损伤和肌动蛋白表面膜极性的丧失。MR-1过表达也增加了MLC-2和MLC激酶的表达和磷酸化，而MR-1沉默和H/R-treatmentcells.Conclusion：总之，这些数据表明，MR-1促进膜表面肌动蛋白极性和保护HK-2细胞免受H/R损伤。其机制可能涉及通过MLC-2的上调和磷酸化快速组织F-肌动蛋白。(C)2014 S. Karger AG，巴塞尔
Background/Aims: Ischemia/reperfusion (I/R) injury is characterized by cytoskeletal reorganization and loss of polarity in proximal tubule epithelial cells. Previously, we showed that myofibrillogenesis regulator (MR)-1 promoted actin organization in cardiomyocytes. MR-1 is also expressed in the kidney.Methods: In this study, we investigated MR-1 expression in acute renal failure induced by I/R in Sprague-Dawley rats. We determined the MR-1 expression and the ratio of fibrous actin (F-actin) to globular actin (G-actin). HK-2 cells were treated with or without hypoxia/reoxygenation (H/R), and MR-1 levels were increased by adenoviral overexpression or silenced by RNA interference.Results: I/R and H/R resulted in cellular injury and decreases of MR-1, the F-/G-actin ratio, and myosin light chain (MLC)-2. MR-1 overexpression attenuated H/R-induced cell injury and loss of surface membrane polarity of actin. MR-1 overexpression also increased the expression and phosphorylation of MLC-2 and MLC kinase, which were decreased in MR-1-silenced and H/R-treated cells.Conclusion: Together, these data show that MR-1 promoted actin polarity on the membrane surface and protected HK-2 cells from H/R injury. The mechanism might involve the rapid organization of F-actin through the upregulation and phosphorylation of MLC-2. (C) 2014 S. Karger AG, Basel