Coordinated expression of beta 1 integrins and transforming growth factor-beta-induced matrix proteins in glomerulonephritis
Kagami, S.; Border, W.A.; Ruoslahti, E.; Noble, N.A.
Laboratory Investigation; a Journal of Technical Methods and Pathology 69(1): 68-76
1993
ISSN/ISBN: 0023-6837 PMID: 8331901 Document Number: 419934
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.