Human mesangial cells secrete a GBM-degrading neutral proteinase and a specific inhibitor.
The factors operative during normal and disease states which govern the degradation of the glomerular extracellular matrix (ECM, glomerular basement membrane and mesangial matrix) remain poorly understood. These structures consist primarily of types IV and V collagen, which are highly resistant to the action of classical interstitial collagenases. Here we report that an intrinsic glomerular cell type, the human mesangial cell, secretes: 1) a neutral proteinase with specific activity against type IV basement membrane collagen and, 2) an inhibitory protein with the characteristics of the tissue inhibitor of metalloproteinases (TIMP). The purified enzyme has a neutral pH optimum, consists of a basic (pI 8.4) protein doublet with molecular weight of 66 and 68 kilodaltons, and is inhibited by calcium and zinc chelators. The enzyme degrades both soluble and basement membrane type IV collagen, but does not specifically degrade types I or V collagen or casein. Immunohistochemistry of cultured cells demonstrated homogeneous staining for the neutral proteinase antigen, while the TIMP antigen was detected in fewer than one-third of cultured cells. These findings suggest that the synthesis of these proteins may be independently regulated. The secretion of these factors may play an important role in the turnover of the glomerular ECM under basal or pathologic conditions.
Martin
J
J
Medical Service, San Francisco VAMC-University of California.
Davies
M
M
Thomas
G
G
Lovett
D H
DH
D001485:Basement Membrane / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D010450:Endopeptidases / Q000302:isolation & purification*; D005109:Extracellular Matrix / Q000378:metabolism; D005920:Glomerular Mesangium / Q000201:enzymology*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism*; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification*; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D010450:Endopeptidases; D008666:Metalloendopeptidases; D003012:Microbial Collagenase; D020780:Matrix Metalloproteinase 9