Transforming growth factor-beta (TGF-beta) stimulates the expression of beta 1 integrins and adhesion by rat mesangial cells

Transforming growth factor-beta (TGF-beta) has been implicated in the pathogenesis of mesangial matrix (MM) accumulation in human and experimental glomerulonephritis. To clarify molecular mechanisms responsible for pathological MM deposition, we examined the effect of TGF-beta on the production of beta 1 integrins and on adhesion function of rat mesangial cells (MC). In immunoprecipitation experiments using [S-35]methionine-labeled MC, stimulation of MC with TGF-beta for 48 h resulted in an increase in the synthesis of alpha 1 beta 1 (collagen/laminin receptor) and alpha 5 beta 1 (fibronectin receptor) integrins accompanied by increases in the synthesis of their Ligands, collagen type I (collagen I), and fibronectin. A time-dependent increase in beta 1, alpha 1 integrin subunit mRNA peaking 48 h after exposure to TGF-beta was shown by Northern blot analysis. After 48 h of treatment with TGF-beta, MC displayed significant increases in adhesion to fibronectin, collagen I, and laminin as compared to untreated MC. Anti-beta 1 antiserum significantly inhibits MC adhesion to fibronectin, collagen I, and laminin. Anti-alpha 1 subunit antibody very strongly inhibited adhesion to collagen I and laminin, but not to fibronectin. Synthetic peptides containing RGD sequences specifically blocked adhesion to fibronectin. These data suggest that TGF-beta may promote MM deposition by increasing MC synthesis of both matrix proteins and beta 1 integrins which facilitate binding of these proteins to the MC surface and thus enhance their incorporation into MRI. (C) 1996 Academic Press, Inc.