COLLAGEN TYPE-I ENHANCES ENDOTHELIN-MEDIATED CONTRACTION AND INDUCES NONPROLIFERATING PHENOTYPE IN MESANGIAL CELLS

Accumulation of glomerular extracellular matrix is a characteristic ac companiment of mesangial cell proliferation in progressive renal disea se. We examined how growth on several matrices affected the proliferat ive phenotype of cultured rat mesangial cells. Compared with growth on plastic, Matrigel, or mesangial matrix, collagen type I caused a decr eased cell number at 72 h, decreased total DNA per culture, and a decr ease in the incorporation of [H-3]thymidine during S phase in cells re leased from quiescence. These antiproliferative and antimitogenic effe cts of collagen type I required growth on a collagen gel; soluble coll agen or collagen fragments were without effect. Because a number of ag ents elicit both proliferative and contractile responses in mesangial cells, we examined the effect of growth on collagen on contractility. Compared with plastic, cells grown on collagen type I were more contra ctile, showed a higher Ca2+ signal in response to endothelin, and resp onded to endothelin with a more rapid myosin light-chain kinase-depend ent phosphorylation of myosin light chain. We conclude that growth on a collagen type I gel uncouples contractility from a proliferative res ponse in mesangial cells, suppressing proliferation while enhancing co ntraction and Ca2+ signaling in response to endothelin.