Modulation of human mesangial cell behaviour by extracellular matrix components--the possible role of interstitial...

We have investigated the effects of various extracellular matrix (ECM) components on the behaviour of human mesangial cells (HMC) in a gel culture system using a modified MTT assay method. When cultured on a reconstituted basement membrane, Matrigel (M gel), HMC aggregated and formed isolated colonies initially, then extended an array of cell processes to form a dendritic network structure and proliferated very slowly as the culture period progressed. On type I collagen gel (CI gel), however, HMC developed elongated bipolar shapes, migrated into the gel, and showed rapid cell growth. Next, separate ECM components, such as type III and IV collagens, laminin, heparin and heparan sulphate, were incorporated into CI gel and HMC proliferation was assessed. Although attachment of HMC to each gel did not differ significantly, HMC proliferation was inhibited markedly on gels containing type III collagen, heparin and heparan sulphate; type IV collagen suppressed HMC proliferation slightly; and laminin had no significant effect. These data suggest that interstitial type I and III collagens, which are often observed in diseased glomeruli, as well as the basement membrane components, may play important roles in the regulation of HMC proliferation under pathophysiological conditions in vivo. We conclude that HMC behaviour is affected by the surrounding ECM constituents, which appear to function as a refined modulator.