RELATIONSHIPS BETWEEN MESANGIAL CELL-PROLIFERATION AND TYPE-I AND TYPE-IV COLLAGEN MESSENGER-RNA LEVELS IN-VITRO

Changes in the composition of the mesangial extracellular matrix (ECM) and cell turnover are present in glomerular disease. To determine if ECM changes play a role in perpetuating mesangial cell dysfunction, we examined a line of mouse mesangial cells cultured on films or gels of several ECM components and also on methyl cellulose, an inert substrate that prevents attachment. Cells on films of fibronectin or type IV or I collagen had persistently high growth rates and high levels of alpha(1)-I and alpha(1)-IV collagen mRNAs. In contrast, on gels of type IV or I collagen or matrigel, the growth rate was low. The alpha(1)-IV collagen mRNA levels were low on type TV collagen gel or matrigel, whereas the alpha(1)-I collagen mRNA levels remained high. In contrast, the alpha(1)-I collagen mRNA levels were low on type I collagen gel, and the alpha(1)-IV collagen mRNA levels were high. Cells on methyl cellulose formed floating aggregates, did not proliferate, and had a 5- to 10-fold decrease in both alpha(1)-I and alpha(1)-IV collagen mRNA levels. These phenotypic changes were largely reversible. Finally, when matrigel was layered over cells on fibronectin films, alpha(1)-IV collagen mRNA levels decreased, but alpha(1)-I collagen mRNA levels and proliferation remained high. Thus proliferation and alpha(1)-I and alpha(1)-IV collagen mRNA levels in mesangial cells were independently regulated and depended on attachment and the nature of the adjacent matrix.