Modulation of mesangial cell migration by extracellular matrix components. Inhibition by heparinlike glycosaminoglycans.

Extension of mesangial cells (MC) into the pericapillary space is a pathologic response seen in several forms of glomerulonephritis. This process may involve both cytoplasmic extension by MC and actual cellular migration. For investigation of whether extracellular matrix factors could modulate this process, the migratory responses of rat MC were quantitatively examined using a cell culture model. Denuding ("wounding") a portion of a confluent culture of MC was followed by migration of mesangial cells into the denuded area. The expected proliferative response to this treatment was blocked by irradiation. The migratory response began within 8 hours of wounding and continued for at least 80 hours. The MC migratory response was specifically inhibited in a dose-dependent and reversible manner by heparin and heparinlike glycosaminoglycans (GAGs). Chondroitin sulfates and hyaluronic acid did not significantly inhibit MC migration. Glomerular basement membrane heparinlike GAGs may normally prevent MC extension into the pericapillary space. Changes in the density or composition of these substances during glomerular inflammatory processes could permit the development of MC pericapillary extensions and thereby lead to further alterations in basement membrane integrity.