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

Lab Invest. 1993 Jul;69(1):68-76.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • Cytokines / pharmacology
  • Extracellular Matrix Proteins / metabolism*
  • Glomerulonephritis / metabolism*
  • Glomerulonephritis / pathology
  • Immunohistochemistry
  • Integrins / metabolism*
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Precipitin Tests
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Cytokines
  • Extracellular Matrix Proteins
  • Integrins
  • Transforming Growth Factor beta