Published online Aug 6, 2013. doi: 10.5527/wjn.v2.i3.84
Revised: August 1, 2013
Accepted: August 3, 2013
Published online: August 6, 2013
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.
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.