Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 299, Issue 5, Pages F973-F982Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00216.2010
Keywords
tubular basement membrane; epithelial-to-myofibroblast transition; collagen
Categories
Funding
- National Science Foundation of China [30470800, 30771010, 30871201]
- Ministry of Science and Technology, China [2006CB503909]
- Jiangsu Province's Outstanding Medical Academic Leader Program [SWKJ 2006-50]
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Wang X, Zhou Y, Tan R, Xiong M, He W, Fang L, Wen P, Jiang L, Yang J. Mice lacking the matrix metalloproteinase-9 gene reduce renal interstitial fibrosis in obstructive nephropathy. Am J Physiol Renal Physiol 299: F973-F982, 2010. First published September 15, 2010; doi:10.1152/ajprenal. 00216.2010.-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)-beta 1 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.
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