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World J Nephrol. Aug 6, 2013; 2(3): 84-89
Published online Aug 6, 2013. doi: 10.5527/wjn.v2.i3.84
Matrix metalloproteinases contribute to kidney fibrosis in chronic kidney diseases
Hong Zhao, Yanting Dong, Xinrui Tian, Thian Kui Tan, Zhuola Liu, Ye Zhao, Yun Zhang, David CH Harris, Guoping Zheng
Hong Zhao, Yanting Dong, Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, Shaanxi Province, China
Xinrui Tian, Zhuola Liu, Department of Respiratory Medicine, the Second Hospital of Shanxi Medical University, Taiyuan 030001, Shaanxi Province, China
Yun Zhang, Experimental Centre of Science and Research, the First Clinical Hospital of Shanxi Medical University, Taiyuan 030001, Shaanxi Province, China
Thian Kui Tan, Ye Zhao, David CH Harris, Guoping Zheng, Centre for Transplantation and Renal Research, Westmead Millennium Institute, the University of Sydney, NSW 2145, Sydney, Australia
Author contributions: ALL authors contributed to this manuscript in writing, study results and approval of the manuscript.
Correspondence to: Guoping Zheng, MD, PhD, Centre for Transplantation and Renal Research, Westmead Millennium Institute, the University of Sydney, City Road, NSW 2145, Sydney, Australia. guoping.zheng@sydney.edu.au
Telephone: +61-2-98459582 Fax: +61-2-98459620
Received: June 29, 2013
Revised: August 1, 2013
Accepted: August 3, 2013
Published online: August 6, 2013
Abstract

Matrix metalloproteinases (MMPs) are members of the neutral proteinase family. They were previously thought to be anti-fibrotic because of their ability to degrade and remodel of extracellular matrix. However, recent studies have shown that MMPs are implicated in initiation and progression of kidney fibrosis through tubular cell epithelial–mesenchymal transition (EMT) as well as activation of resident fibroblasts, endothelial-mesenchymal transition (EndoMT) and pericyte-myofibroblast transdifferentiation. Interstitial macrophage infiltration has also been shown to correlate with the severity of kidney fibrosis in various chronic kidney diseases. MMPs secreted by macrophages, especially MMP-9, has been shown by us to be profibrotic by induction of tubular cells EMT. EMT is mainly induced by transforming growth factor-β (TGF-β). However, MMP-9 was found by us and others to be up-regulated by TGF-β1 in kidney tubular epithelial cells and secreted by activated macrophages, resulting in EMT and ultimately kidney fibrosis. Therefore, MMP-9 may serve as a potential therapeutic target to prevent kidney fibrosis in chronic kidney disease. This review, by a particular focus on EMT, seeks to provide a comprehensive understanding of MMPs, especially MMP-9, in kidney fibrosis.

Keywords: Matrix metalloproteinase, Chronic kidney disease, Kidney fibrosis, Epithelial–mesenchymal transition Transforming growth factor-β

Core tip: Matrix metalloproteinases (MMPs) were previously known to be anti-fibrotic for their ability to degrade and remodel extracellular matrix proteins. Recent studies including our own have shown that MMPs are implicated in initiation and progression of kidney fibrosis. MMP-9 of both tubular and macrophage origins were found to be able to induce epithelial-mesenchymal transition of tubular cells, an important mechanism causing kidney fibrosis. This review, by focus on MMP-9 and epithelial–mesenchymal transition, seeks to provide a comprehensive understanding for the roles of MMPs in kidney fibrosis.