[Epithelial-mesenchymal transition in kidney grafts].
Late loss of renal grafts is primarily due to progressive sclerosis, involving both immune and non immune processes. Activation of interstitial fibroblasts responsible for graft fibrosis is known to involve proliferation and activation of resident fibroblasts, recruitment of bone marrow-derived stem cells, and epithelial-mesenchymal transition, a more recently identifled mechanism. In this latter process, tubular epithelial cells lose their epithelial phenotype, acquire mesenchymal markers and properties, and participate in the fibrotic process. Whether or not these cells move into the interstitium is controversial. By using immunohistochemistry with specific antibodies against vimentin, beta cadherin, beta catenin and other fibroblastic markers, we found that tubular epithelial cells in kidney grafts can exhibit phenotypic markers of epithelial-mesenchymal transition as early as 3 months after transplantation, before the onset of fibrosis. These changes are associated with prolonged cold ischemia and clinical or subclinical acute rejection. In addition, changes observed at 3 months seem to be predictive of both the fibrosis score at 12 months and, interestingly, the progression of fibrosis between 3 months and 12 months. Finally, renal function at 2 years was significantly poorer in patients exhibiting epithelial changes at 3 months. These results suggest that the epithelial-mesenchymal transition plays a role in the progressive fibrosis of kidney grafts, and that its early inhibition could prevent the gradual decline in renal function and late graft loss.
Rondeau
Eric
E
Urgences Néphrologiques et Transplantation rénale, et INSERM UMRS 702, Hôpital Tenon, 4 rue de la Chine, 75020 Paris. eric.rondeau@tnn.aphp.fr
Hertig
Alexandre
A
Rafat
Cédric
C
Xu-Dubois
Yi-chun
YC
D002454:Cell Differentiation; D004847:Epithelial Cells / Q000473:pathology*; D005347:Fibroblasts / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000473:pathology*; D016030:Kidney Transplantation