Coordinated expression of beta 1 integrins and transforming growth factor-beta-induced matrix proteins in glomerulonephritis.

BACKGROUND

Extracellular matrix remodeling after tissue injury involves both cell-cell and cell-matrix interactions. Integrins are matrix receptors that play a central role in such interactions, and transforming growth factor-beta (TGF-beta) is known to be a strong modulator of their expression. Our previous work has shown that in the anti-thymocyte serum-induced model of glomerulonephritis in the rat, elevated glomerular production of TGF-beta is a causal factor in matrix accumulation. Here we present data on the expression and distribution of glomerular beta 1 integrins in experimental glomerulonephritis.

EXPERIMENTAL DESIGN

Metabolic labeling, immunohistochemical, and immunoprecipitation techniques were used on kidney glomeruli from normal rats and from rats over the course of glomerulonephritis induced by administration of anti-thymocyte serum. Changes in beta 1 subunit-containing integrins and the extracellular matrix components that serve as ligands for these integrins were characterized.

RESULTS

The data indicate that expression in glomeruli of alpha 1, alpha 5, and beta 1 subunits paralleled both mesangial content of the ligands for the alpha 1 beta 1 and alpha 5 beta 1 integrins, laminin, collagen and fibronectin, and TGF-beta 1 protein; increasing on day 7 of disease and decreasing toward normal by day 28. The alpha 3 subunit displayed the opposite pattern. Exogenous TGF-beta, but not other cytokines, stimulated synthesis of alpha 1 beta 1 and alpha 5 beta 1 integrins by normal glomeruli.

CONCLUSIONS

The data indicate that glomerular beta 1 integrin expression is altered in a manner that would promote cell adhesion to the matrix proteins known to accumulate in this disease model. The data further suggest that TGF-beta is responsible for these changes.