Transforming growth factor-beta 1 enhances glomerular collagen synthesis in diabetic rats.
In vitro glomerular collagen synthesis and its response to various concentrations of transforming growth factor-beta 1 were studied in normal and diabetic rats. TGF-beta 1 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-beta 1 had no effect. Antibody to TGF-beta 1 prevented this increase in collagen synthesis. Both circulating TGF-beta 1 concentration and its glomerular expression of mRNA were higher in diabetic than in normal rats. Although addition of TGF-beta 1 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-beta 1 in renal glomerular collagen synthesis in the normal rat, and suggests a possible causal role for enhanced collagen synthesis in the diabetic rat.
Bollineni
J S
JS
Department of Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103.
Reddi
A S
AS
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D003094:Collagen / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D007678:Kidney Glomerulus / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000097:blood / Q000235:genetics / Q000494:pharmacology*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen