| First Author | Du X | Year | 2012 |
| Journal | Lab Invest | Volume | 92 |
| Issue | 8 | Pages | 1149-60 |
| PubMed ID | 22614125 | Mgi Jnum | J:186841 |
| Mgi Id | MGI:5433417 | Doi | 10.1038/labinvest.2012.68 |
| Citation | Du X, et al. (2012) Involvement of matrix metalloproteinase-2 in the development of renal interstitial fibrosis in mouse obstructive nephropathy. Lab Invest 92(8):1149-60 |
| abstractText | Renal fibrosis is a common finding in progressive renal diseases. Matrix metalloproteinases (MMPs) are involved in epithelial-to-mesenchymal transition (EMT). We investigated the role of MMP-2 and the effect of inhibition of MMPs on the development of renal fibrosis. Renal fibrosis was induced in MMP-2 wild-type (MMP-2(+/+)) mice by unilateral ureteral obstruction (UUO). Renal histopathology, EMT-associated molecules, and activity of MMP-2 and MMP-9 were examined during the development of interstitial fibrosis. UUO-renal fibrosis was also induced in MMP-2 deficient (MMP-2(-/-)) and MMP-2(+/+) mice treated with minocycline (inhibitor of MMPs). In MMP-2(+/+) mice, MMP-2 and MMP-9 were expressed in damaged tubules, and their activities increased in a time-dependent manner after UUO. Interstitial fibrosis was noted at day 14, with deposition of types III and I collagens and expression of markers of mesenchymal cells (S100A4, vimentin, alpha-smooth muscle actin, and heat shock protein-47) in damaged tubular epithelial cells, together with F4/80+ macrophage infiltration. Fibrotic kidneys expressed EMT-associated molecules (ILK, TGF-beta1, Smad, Wnt, beta-catenin, and Snail). In contrast, the kidneys of MMP-2(-/-) mice and minocycline-treated MMP-2(+/+) mice showed amelioration of renal fibrosis with reduced expression of markers of mesenchymal cells in tubular epithelial cells, inhibition of upregulated EMT-associated molecules, and suppression of macrophage infiltration. The results suggested that MMP-2 have a pathogenic role in renal interstitial fibrosis, possibly through the induction of EMT and macrophage infiltration. Inhibition of MMPs may be beneficial therapeutically in renal fibrosis. |
