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.