Expression of TGFβ-1 and type I TGFβ-receptor on sequential biopsies of renal transplants with chronic allograft nephropathy

The aim of this study was to determine the expression of transforming growth factor-beta (TGF beta)-1 and type I TGF beta-receptor on sequential biopsies from renal transplants with and without chronic allograft nephropathy. Twenty-four renal transplant recipients entered the study. They underwent sequential biopsies performed before (T1: 1.44 +/- 1.2 months) and 6 months after (T2: 15.96 +/- 7.2 months) transplantation. Lesions were graded according to the criteria of the Banff classification. C4d was detected by fluorescence microscopy. Immunohistochemistry was performed in order to identify cells expressing TGF beta-1 and type I TGF beta-receptor. In normal renal tissue (n = 4), TGF beta-1 is expressed by tubular epithelial cells and endothelial cells lining glomerular and peritubular capillaries, whereas type I TGF beta-receptor is expressed by tubular epithelial cells and smooth muscle cells in the media of arteries. In recipients with chronic allograft nephropathy (group 1, n = 14), diffuse epithelial expression of both molecules was found in more patients at T2 than at T1 (42.8% vs 21.4%). In contrast, this pattern of expression remained stable or decreased over time in recipients with long-term normal transplants (group 2, n = 10). Furthermore, type 1 TGF beta-receptor was detected on the smooth muscle cells of arteries in 12/14 (85.7%) of recipients in group I and only in 4/9 (44.4%) of recipients in group 2. No relationship was noticed with regard to C4d deposits. These data suggest that the synthesis of TGF beta-1 and type I TGF beta-receptor increases over time in recipients developing chronic allograft nephropathy. Further studies are in progress in order to quantify mRNA of both molecules with real-time polymerase chain reaction.