Rat mesangial cells express two unique isoforms of laminin which modulate mesangial cell phenotype

Rat mesangial cells express two unique isoforms of laminin which can be modulated by culture medium composition. To define further the nature of laminin expressed by cultured rat mesangial cells, synthesis of individual laminin chains, as well as their trimeric association, was examined. Based on data from Northern analysis of mRNA expression, immunoblots, immunofluorescence staining and radioimmunoprecipitation of biosynthetically labeled proteins, mesangial cells express laminin β1, β2, and γ1 chains. Mesangial cells do not express laminin α1 or α2. MC produce a unique α chain, designated α′m. These laminin chains assemble into two major isoforms. One contains α′mβ1γ1, co-precipitates with entactin and is assembled into the fibrillar extracellular matrix. The second isoform contains α′mβ2 and a presumed γ chain that migrates in gel slightly ahead of γ1. The β2-containing isoform is concentrated in punctate sites on the cell surface. In addition, mesangial cells display different phenotypes when plated on laminin-1 (α1β1γ1), as compared to purified β2. An LRE-containing peptide of laminin β2 serves as an attachment site for mesangial cells and is sufficient to induce the phenotype observed with intact β2. These data suggest that laminin isoform expression plays an important role in mesangial cell phenotype and function.