title: Matrix metalloproteinases contribute to kidney fibrosis in chronic kidney diseases.
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.
authors.affiliation: Hong Zhao, Yanting Dong, Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, Shaanxi Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Yanting
authors.initials: Y
authors.lastname: Dong
authors.forename: Xinrui
authors.initials: X
authors.lastname: Tian
authors.forename: Thian Kui
authors.initials: TK
authors.lastname: Tan
authors.forename: Zhuola
authors.initials: Z
authors.lastname: Liu
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: David Ch
authors.initials: DCh
authors.lastname: Harris
authors.forename: Guoping
authors.initials: G
authors.lastname: Zheng
keywords: Chronic kidney disease; Epithelial–mesenchymal transition Transforming growth factor-β; Kidney fibrosis; Matrix metalloproteinase