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蛋白激酶G和活性氧在健康与疾病状态下对足细胞功能调节中的作用

Role of Protein Kinase G and Reactive Oxygen Species in the Regulation of Podocyte Function in Health and Disease.

作者信息

Piwkowska Agnieszka

机构信息

Mossakowski Medical Research Centre Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdańsk, Poland.

出版信息

J Cell Physiol. 2017 Apr;232(4):691-697. doi: 10.1002/jcp.25613. Epub 2016 Sep 30.

Abstract

Podocytes and their foot processes form an important cellular layer of the glomerular barrier involved in the regulation of glomerular permeability. Disturbing the function of podocytes plays a central role in the development of proteinuria in diabetic nephropathy. Retraction of the podocyte foot processes that form slit diaphragms is a common feature of proteinuria; although, the correlation between these events in not well understood. Notably, it is unclear whether podocyte foot processes are able to regulate slit diaphragm permeability and glomerular ultrafiltration. The occurrence of reactive oxygen species generation, insulin resistance, and hyperglycemia characterizes early stages of type 2 diabetes. Protein kinase G type I alpha (PKGIα) is an intracellular target for vasorelaxant factors. It is activated in both cGMP-dependent and cGMP-independent manners. Recently, we demonstrated a relationship between oxidative stress, PKGIα activation, actin reorganization, and changes in the permeability of the filtration barrier. This review discusses how redox imbalance affects both the activity of PKGIα and PKGI-dependent signaling pathways in podocytes. J. Cell. Physiol. 232: 691-697, 2017. © 2016 Wiley Periodicals, Inc.

摘要

足细胞及其足突构成肾小球屏障的重要细胞层,参与肾小球通透性的调节。足细胞功能紊乱在糖尿病肾病蛋白尿的发生中起核心作用。形成裂孔隔膜的足细胞足突回缩是蛋白尿的常见特征;尽管这些事件之间的关联尚未完全清楚。值得注意的是,尚不清楚足细胞足突是否能够调节裂孔隔膜通透性和肾小球超滤。活性氧生成、胰岛素抵抗和高血糖的出现是2型糖尿病早期阶段的特征。蛋白激酶G Iα型(PKGIα)是血管舒张因子的细胞内靶点。它以cGMP依赖和cGMP非依赖的方式被激活。最近,我们证明了氧化应激、PKGIα激活、肌动蛋白重组与滤过屏障通透性变化之间的关系。本综述讨论了氧化还原失衡如何影响足细胞中PKGIα的活性和PKGI依赖的信号通路。《细胞生理学杂志》232: 691 - 697, 2017。© 2016威利期刊公司

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