DEDICATION To my children Iskra and IstokExtracellular Matrix Affects Mesangial Cell Phenotype Effect Of Collagen Type I and Heparin on Cell Proliferation and Contractility

Accumulation of extracellular matrix (ECM) in renal disease is accompanied by a switch in mesangial cell (MC) phenotypes. From quiescent they become proliferative, from contractile they become hypocontrdctile, and accgmulate proteoglycans (PG) and collagen type I (collagen) among other ECM components. Heparin, a glycosaminoglycan related to heparan sulfate PGs, and collagen both suppress MC proliferation. We tested the hypothesis that heparin and collagen regulate MC phenotypes by affecting intracellular kinase cnscades. Compared with growth on plastic, Matrigel, or mesangial matrix, collagen decreased cell number, total DNA per culture, mitogenic response, and c-fos induction. Intact collagen was required for these effects. Soluble collagen fragments were ineffective. Collagen decreased activation of mitogen-activated protein kinase (MAPK) by phorbol ester (TPA) or serum, or of Ca2+/calmodulin-dependent kinase (CaMK)-I1 by ionomycin. Loss of PKC activity upon trypsinization was restored in cells attached to plastic but not in cells on collagen. Collagen inhibited global phosphorylation of tyrosine in contrast to cells on plastic. Compared with plastic, cells grown on collagen were more contractile, showed a higher Ca2+ signal, an