Collagen type I modulates the platelet-derived growth factor (PDGF) regulation of the growth and expression of β1 integrins by rat mesangial cells

Mesangial cell (RLC) proliferation and the deposition of collagen type I (collagen I) are the major pathological features in many types of glomerulonephritis (GN). Recent work suggested that beta-integrins play a critical role in the cell proliferation and extracellular matrix (ECM) remodeling observed in tissue repair after injury. To examine the involvement of beta-integrins in MC proliferation in association with the interaction of MCs with pathological collagen I, we investigated the effect of a prominent mitogen, platelet-derived growth factor-BE (PDGF-EE) on the growth and expression of beta-integrins by MCs cultured on plastic or in a three-dimensional collagen I gel. Immunoprecipitation using S-35-metabolic labeling, flow cytometry and a H-3-thymidine-uptake analysis demonstrated that PDGF-BB stimulated the cell mitogenicity and the expression of alpha 5 beta 1 integrin (a fibronectin receptor), but not alpha 1 beta 1 integrin (a collagen and laminin receptor) of MCs on plastic, in a dose-dependent manner. In contrast, MCs in the collagen I gels showed no significant changes in mitogenicity or alpha 1 beta 1 and alpha 5 beta 1 integrin expression, but increased alpha 1 beta 1 integrin-mediated gel contraction was observed after PDGF-BE stimulation. Thus, the parallel up-regulation of MC-mitogenicity and alpha 5 beta 1 integrin expression by PDGF-BB suggested that alpha 5 beta 1 integrin is an important ECM receptor involved in the proliferative phenotype of MC. A spatial interaction between MCs and pathological collagen I in GN may influence the PDGF regulation of the MC phenotype regarding the cell growth and the expression of beta 1 integrins. (C) 1998 Academic Press.