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Updated: Jun 8, 2026
The Mouse Isolated Perfused Kidney Technique
Published on: November 17, 2016
Mice lacking the matrix metalloproteinase-9 gene reduce renal interstitial fibrosis in obstructive nephropathy
Xiaohua Wang1, Yang Zhou, Ruoyun Tan
1Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical Univ., 262 Zhongshan East Rd., Nanjing 210003, Jiangsu Province, China.
Abstract:
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)-β1 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.
Insights
Matrix metalloproteinase-9 (MMP-9) deficiency protects against kidney fibrosis by preventing tubular basement membrane damage and epithelial-to-myofibroblast transition. This highlights MMP-9
Area of Science:
- Nephrology
- Molecular Biology
- Pathology
Background:
- The role of matrix metalloproteinase-9 (MMP-9) in renal interstitial fibrosis is not well understood.
- Renal interstitial fibrosis is a common pathway for progressive kidney diseases.
- Obstructive nephropathy is a model for studying kidney fibrosis.
Purpose of the Study:
- To investigate the role of MMP-9 in the pathogenesis of renal interstitial fibrosis.
- To determine if MMP-9 contributes to kidney injury and fibrosis in obstructive nephropathy.
Main Methods:
- Utilized a mouse model of obstructive nephropathy.
- Compared wild-type mice with mice lacking MMP-9 (MMP-9 knockout).
- Assessed kidney injury, tubular basement membrane (TBM) integrity, fibronectin expression, collagen deposition, and epithelial-to-myofibroblast transition (EMT).
Main Results:
- Mice lacking MMP-9 showed attenuated renal interstitial fibrotic lesions and morphological injury.
- MMP-9 deficiency reduced TBM disruption, fibronectin expression, and collagen deposition in obstructed kidneys.
- MMP-9 deficiency blocked tubular EMT but did not affect TGF-β1 axis induction; in vitro studies showed MMP-9-digested TBM promotes EMT.
Conclusions:
- Matrix metalloproteinase-9 plays a detrimental role in renal interstitial fibrogenesis.
- MMP-9 contributes to fibrosis by causing TBM destruction, which promotes EMT.
- Ablation of MMP-9 offers a protective effect against kidney fibrosis in obstructive nephropathy.
