Transforming growth factor-beta and its receptors in rabbit renal proximal tubules after uninephrectomy

Transforming growth factor-β (TGFβ) and its receptors were studied in proximal tubules isolated from rabbit renal cortex at different times after uninephrectomy (UNX). Scatchard analysis of TGFβ-binding data in proximal tubules from control kidneys revealed two types of 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 or 2 weeks after either UNX or sham operation (SNX). However, B(max) increased in parallel with the observed increase in the protein/DNA ratio of the proximal tubules at 2 weeks after UNX. In contrast, [¹²⁵I]-insulin binding per milligram of protein was lower in proximal tubules from uninephrectomized compared to sham-operated animals within the same time period. Affinity labeling of [¹²⁵I]-TGFβ₁-binding sites in proximal tubules from either sham- operated or uninephrectomized rabbits displayed two labeled proteins with apparent molecular weights of >143 and 43 kD. We found an increased TGFβ bioactivity in the conditioned medium of proximal tubules at 2 weeks following UNX. This protein increase was associated with an increased TGFβ₁ mRNA expression in these tubules. In contrast, no significant changes in TGFβ bioactivity were observed in rabbit glomeruli conditioned medium or in rabbit urine at this time period after UNX. Our data indicate that hypertrophy of the proximal tubule is associated with an increased TGFβ production and a lack of downregulation of its receptors in this nephron portion.