Nephrol Dial Transplant (2000) 15: 191-199
© 2000 European Renal Association-European Dialysis and Transplant Association
Immunoelectron microscopic study on type I, II and III TGF-ß receptors on visceral glomerular epithelial cells in relation to glomerular basement membrane alterations in proteinuric rats
1 First Department of Medicine, Hamamatsu University School of Medicine, 2 Division of Nephrology, Seirei Hamamatsu General Hospital, Hamamatsu and 3 Department of Medicine, Teikyo University School of Medicine, Itabashi, Tokyo, Japan
Correspondence and offprint requests to: Yoshihide Fujigaki, MD, First Department of Medicine, Hamamatsu University School of Medicine, Handa-cho 3600, 431–3192 Hamamatsu, Japan.
Background. Transforming growth factor (TGF)-ß is a regulator of extracellular matrix accumulation. Both TGF-ß receptors, type I (TßRI) and type II (TßRII), may be required for signal transduction in the TGF-ß pathway. The aim of this study was to investigate the relationship between the TGF-ß pathways and glomerular basement membrane (GBM) accumulation in vivo.
Methods. We examined TßRI, 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 anti-thymocyte 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 TßRI was not detected on GEP, TßRII expression was very occasionally found on GEP and TßRIII was seen in the cytoplasm of the GEP. TßRI, TßRII, and TßRIII were constitutively expressed on glomerular endothelial cells. By day 3 of anti-GBM nephritis and PHN, expression of TßRI, TßRII, and TßRIII 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 TßRI and TßRII on GEP increased in association with GBM thickening. Expression of TßRIII 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 TßRI and TßRII on GEP was noted, but from day 7 onwards, expression of TßR II on GEP dramatically decreased. Expression of TßRIII 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 TßRI, TßRII and possibly TßRIII on GEP may contribute to GBM matrix accumulation in vivo.
Keywords: glomerular basement membrane; glomerular epithelial cell; glomerulonephritis; TGF-ß; TGF-ß receptor
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