No abstract

The role of the glomerular visceral epithelial cell in the physiologic turnover and pathologic breakdown of the glomerular extracellular matrix has remained largely unexplored. In this study a 98-kD neutral proteinase secreted by cultured rat visceral glomerular epithelial cells was shown to be a calcium, zinc-dependent enzyme secreted in latent form. In addition, the protein was heavily glycosylated and demonstrated proteolytic activity against Type I gelatin, Type IV collagen gelatin, and fibronectin. The similarity in molecular mass and substrate specificities to the 92-kD human matrix metalloproteinase-9 (MMP-9, or gelatinase B) suggested the identity of this activity, which was confirmed by immunoprecipitation and Northern blot analysis. The differences in molecular mass (98 vs. 92 kD) were not due to species-specific differences in glycosylation patterns, since cultured rat peritoneal macrophages secreted MMP-9 as a 92-kD enzyme. Furthermore, transfection of the human MMP-9 cDNA into rat glomerular epithelial cells yielded the 98-kD product. Using a specific monoclonal anti-MMP-9 antibody and in situ reverse transcription (ISRT) analysis of MMP-9 mRNA, the expression of this enzyme was evaluated in vivo. Normal rat glomeruli expressed little immunohistochemical or ISRT staining for MMP-9, while in rats with passive Heymann nephritis there was a major increase in MMP-9 protein and mRNA staining within the visceral epithelial cells. The temporal patterns of MMP-9 expression correlated with the period of proteinuria associated with this model, suggesting that a causal relationship may exist between GEC MMP-9 expression and changes in glomerular capillary permeability. ( J. Clin. Invest. 1996. 97:1094-1101.)

No abstract

The matrix metalloproteinases (MMPs) are all members of a highly conserved supergene family that consists of proteolytic enzymes capable of specific extracellular matrix protein interactions. The 92 kDa MMP-9 (gelatinase B) has been extensively characterized at the structural level and shown to degrade specifically the gelatins derived from basement membrane types IV and V collagens (Wilhelm et al., 1989; Mackay et aI., 1990;Morodomi et al., 1992). The closely related 72 kDa MMP-2 (gelatinase A) has a similar enzymatic spectrum, but may be distinguished from MMP-9 on the basis of cellular sources and patterns of induction. Both enzymes have been observed within the culture supernates of numerous cell types, including fibroblasts, endothelial cells and monocyte/macrophages, as well as tumor cells of diverse origin (Wilhelm et al.,