Immunoelectron microscopic study on type I, II and III TGF-β receptors on visceral glomerular epithelial cells in relation to glomerular basement membrane alterations in proteinuric rats

Background. Transforming growth factor (TGF)-beta is a regulator of extracellular matrix accumulation. Both TGF-beta receptors, type I (T beta RI) and type II (T beta RII), may be required for signal transduction in the TGF-beta pathway. The aim of this study was to investigate the relationship between the TGF-beta pathways and glomerular basement membrane (GBM) accumulation in vivo. Methods. We examined T beta RI, II, and III protein expression on visceral glomerular epithelial cells (GEP) in relation to GBM alterations in passive Heymann nephritis (PHN), anti-GBM nephritis and antithymocyte serum (ATS) nephritis. Renal tissues were examined by pre-embedding immunoelectron microscopy 3, 7 and 14 days after induction of nephritis in rats. Results. In normal control rats T beta RI was not detected on GEP, T beta RII expression was very occasionally found on GEP and T beta RIII was seen in the cytoplasm of the GEP. T beta RI, T beta RII, and T beta RIII were constitutively expressed on glomerular endothelial cells. By day 3 of anti-GBM nephritis and PHN, expression of T beta RI, T beta RII, and T beta RIII was still similar to that of normal control rats, and GBM alterations in both models were not prominent except for deposit formation in PHN. From day 7 onwards, in both models, expression of T beta RI and T beta RII on GEP increased in association with GBM thickening. Expression of T beta RIII in the cytoplasm of the GEP was increased, with occasional positive staining being seen on the urinary surface of the GEP from day 7 onwards. On the other hand, at day 3 of ATS nephritis, increased expression of T beta RI and T beta RII on GEP was noted, but from day 7 onwards, expression of TPR II on GEP dramatically decreased. Expression of T beta RIII in the cytoplasm of the GEP also transiently increased at day 3. GBM thickening was not noted in ATS nephritis. Conclusions. The results suggest that persistent upregulation of expression of T beta RI, T beta RII and possibly T beta RIII on GEP may contribute to GBM matrix accumulation in vivo.