Expression of TGFbeta-1 and Type I TGFbeta-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 (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.
Martin
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Department of Pathology, Faculty of Medicine, 7 boulevard Jeanne d'Arc, 21079 Dijon Cedex, France. laurent.martin@u-bourgogne.fr
Guilbeau
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Bocrie
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Rageot
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Rifle
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Justrabo
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Mousson
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D030201:Activin Receptors, Type I / Q000235:genetics*; D001706:Biopsy; D002908:Chronic Disease; D005500:Follow-Up Studies; D006801:Humans; D016030:Kidney Transplantation / Q000473:pathology* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000473:pathology; D011183:Postoperative Complications / Q000276:immunology / Q000473:pathology; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012079:Renal Circulation; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D019459:Urothelium / Q000276:immunology / Q000473:pathology
D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I