SPARC IS EXPRESSED BY MESANGIAL CELLS IN EXPERIMENTAL MESANGIAL PROLIFERATIVE NEPHRITIS AND INHIBITS PLATELET-DERIVED-GROWTH-FACTOR-MEDIATED MESANGIAL CELL-PROLIFERATION IN-VITRO

Mesangial cell proliferation is a characteristic feature of many glome rular diseases and often precedes extracellular matrix expansion and g lomerulosclerosis. This study provides the first evidence that SPARC ( secreted protein acidic and rich in cysteine) could be an endogenous f actor mediating resolution of experimental mesangial proliferative nep hritis in the rat, SPARC is a platelet-derived-growth-factor-binding g lycoprotein that inhibits proliferation of endothelial cells and fibro blasts. We now show that SPARC is synthesized by mesangial cells kr cu lture and that SPARC mRNA levels are increased by platelet-derived gro wth factor and basic fibroblast growth factor. Recombinant SPARC or th e synthetic SPARC peptide 2.1 inhibited platelet-derived-growth-factor -induced mesangial cell DNA synthesis in vitro In a model of experimen tal mesangioproliferative glomerulonephritis, SPARC mRNA was increased 5-fold by day 7 and was identified in the mesangium by in situ hybrid ization, Similarly, SPARC was increased in glomerular mesangial cells and visceral epithelial cells by day 5 and reached maximal expression levels by day 7, Mesangial cell proliferation increased by 36-fold on day 5 and decreased abruptly on day 7, Maximal expression of SPARC was correlated with the resolution of mesangial cell proliferation. We pr opose that SPARC functions in part as an endogenous inhibitor of plate let-derived-growth-factor-mediated mesangial cell proliferation in glo merulonephritis and that it could account for the resolution of cellul ar proliferation in this disease.