Renal interstitial fibrosis (RIF) is the end result of chronic kidney disease (CKD) and is predictive of long-term renal survival and its inhibition might delay progression towards end-stage renal disease (ESRD). Since type IV collagen-rich extracellular matrix is replaced by type-1 collagen after injury, the hypothesis is being tested that matrix metalloproteinase-2 (MMP-2), a type IV collagenase, may play a causative role in renal fibrosis. Mechanistic studies are underway using an MMP-2 -/- mouse to determine whether MMP-2 promotes renal tubular epithelial-mesenchymal transition (EMT), myofibroblast proliferation and fibrogenesis with and without unilateral ureteral obstruction (UUO), a murine model of RIF.
In addition, the role of MMP-2 in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) is under study comparing MMP-2 and fibrognesis marker gene and protein expression by human ADPKD epithelia versus normal renal tubular cell lines in vitro.
