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

Transplant Proc. 2006 Sep;38(7):2327-9. doi: 10.1016/j.transproceed.2006.07.009.

Abstract

The aim of this study was to determine the expression of transforming growth factor-beta (TGFbeta)-1 and type I TGFbeta-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 TGFbeta-1 and type I TGFbeta-receptor. In normal renal tissue (n = 4), TGFbeta-1 is expressed by tubular epithelial cells and endothelial cells lining glomerular and peritubular capillaries, whereas type 1 TGFbeta-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 TGFbeta-receptor was detected on the smooth muscle cells of arteries in 12/14 (85.7%) of recipients in group 1 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 TGFbeta-1 and type I TGFbeta-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.

MeSH terms

  • Activin Receptors, Type I / genetics*
  • Biopsy
  • Chronic Disease
  • Follow-Up Studies
  • Humans
  • Kidney Transplantation / pathology*
  • Kidney Transplantation / physiology
  • Muscle, Smooth, Vascular / immunology
  • Muscle, Smooth, Vascular / pathology
  • Postoperative Complications / immunology
  • Postoperative Complications / pathology
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / genetics*
  • Renal Circulation
  • Time Factors
  • Transforming Growth Factor beta1 / genetics*
  • Urothelium / immunology
  • Urothelium / pathology

Substances

  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Protein Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I