| First Author | Wang X | Year | 2010 |
| Journal | Am J Physiol Renal Physiol | Volume | 299 |
| Issue | 5 | Pages | F973-82 |
| PubMed ID | 20844022 | Mgi Jnum | J:165577 |
| Mgi Id | MGI:4837778 | Doi | 10.1152/ajprenal.00216.2010 |
| Citation | Wang X, et al. (2010) Mice lacking the matrix metalloproteinase-9 gene reduce renal interstitial fibrosis in obstructive nephropathy. Am J Physiol Renal Physiol 299(5):F973-82 |
| abstractText | Matrix metalloproteinase-9 (MMP-9) is one of the major components of the matrix proteolytic network, and its role in the pathogenesis of renal interstitial fibrosis remains largely unknown. Here, we demonstrate that ablation of MMP-9 attenuated renal interstitial fibrotic lesions in obstructive nephropathy. Mice lacking MMP-9 were less likely to develop morphological injury, which was characterized by a reduced disruption of tubular basement membrane (TBM) and expression of fibronectin as well as deposition of total tissue collagen in the kidneys after sustained ureteral obstruction compared with their wild-type counterparts. Deficiency of MMP-9 blocked tubular epithelial-to-myofibroblast transition (EMT) but did not alter the induction of transforming growth factor (TGF)-beta1 axis expression in the obstructed kidneys. In vitro, TBM, which was digested by MMP-9 instead of MMP-9 itself, induces EMT and enhances migration of transformed cells. Thus increased MMP-9 is detrimental in renal interstitial fibrogenesis through a cascade of events that leads to TBM destruction and in turn to promotion of EMT. Our findings establish a crucial and definite importance of MMP-9 in the pathogenesis of renal interstitial fibrosis at the whole-animal level. |
