Transforming Growth Factor-β1 Enhances Glomerular Collagen Synthesis in Diabetic Rats

  1. Alluru S Reddi
  1. Department of Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School Newark, New Jersey
  1. Address correspondence and reprint requests to Dr. Alluru S. Reddi, Department of Medicine, UMDNJ-New Jersey Medicine School, 185 South Orange Avenue, Newark, NJ 07103.

Abstract

In vitro glomerular collagen synthesis and its response to various concentrations of transforming growth factor-β1 were studied in normal and diabetic rats. TGF-β1 increased collagen synthesis in normal glomeruli in a dose-dependent manner up to 5 ng/ml. Concentrations > 5 ng/ml showed a gradual decline in collagen synthesis. Basal collagen synthesis was increased in diabetic glomeruli, but addition of TGF-β 1 had no effect. Antibody to TGF-β1 prevented this increase in collagen synthesis. Both circulating TGF-β1 concentration and its glomerular expression of mRNA were higher in diabetic than in normal rats. Although addition of TGF-β1 did not increase synthesis in vitro, the absence of an effect is consistent with downregulation of its receptors attributable to the high circulating levels. This study clearly indicates a regulatory role of TGF-β1 in renal glomerular collagen synthesis in the normal rat, and suggests a possible causal role for enhanced collagen synthesis in the diabetic rat.

  • Received April 7, 1993.
  • Revision received July 1, 1993.
  • Accepted July 1, 1993.
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