TRANSFORMING GROWTH-FACTOR-BETA AND ITS RECEPTORS IN RABBIT RENAL PROXIMAL TUBULES AFTER UNINEPHRECTOMY

Transforming growth factor-beta (TGF beta) and its receptors were stud ied in proximal tubules isolated from rabbit renal cortex at different times after uninephrectomy (UNX). Scatchard analysis of TGF beta-bind ing data in proximal tubules from control kidneys revealed two types o f binding sites, with K-d 21 and 208 pM, and B-max 33 and 104 fmol/mg protein, respectively. K-d values were similar in these animals at 1 o r 2 weeks after either UNX or sham operation (SNX). However, B-max inc reased in parallel with the observed increase in the protein/DNA ratio of the proximal tubules at 2 weeks after UNX. In contrast, [I-125]-in sulin binding per milligram of protein was lower in proximal tubules f rom uninephrectomized compared to sham-operated animals within the sam e time period. Affinity labeling of [I-125]-TGF beta(1)-binding sites in proximal tubules from either sham-operated or uninephrectomized rab bits displayed two labeled proteins with apparent molecular weights of >143 and 43 kD. We found an increased TGF beta bioactivity in the con ditioned medium of proximal tubules at 2 weeks following UNX. This pro tein increase was associated with an increased TGF beta(1) mRNA expres sion in these tubules. In contrast, no significant changes in TGF beta bioactivity were observed in rabbit glomeruli conditioned medium or i n rabbit urine at this time period after UNX. Our data indicate that h ypertrophy of the proximal tubule is associated with an increased TGF beta production and a lack of downregulation of its receptors in this nephron portion.