Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2013
Expression of the transcriptional regulator snail1 in kidney transplants displaying epithelial-to-mesenchymal transition features.
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Xu-Dubois Yi-Chun, Galichon Pierre, Brocheriou Isabelle, Baugey Edith, Morichon Romain, Jouanneau Chantal, Ouali Nacera, Rondeau Eric, Hertig Alexandre
Аннотация
BACKGROUND: The epithelial response to injury is stereotypical and reminiscent of epithelial-to-mesenchymal transitions (EMTs), such as those observed during embryogenesis and tumour metastasis. In the context of solid organ transplantation, EMT-like features are often acquired by epithelial cells and are predictive of graft fibrosis. Here, we studied the possible involvement of several major transcriptional regulators, including snail1, phospho-Smad 2/3 and zeb1, in EMT induction in human renal grafts.
METHODS: We used immunohistochemistry to detect the presence of these EMT transcriptional regulators along with that of two validated EMT markers (intra-cytoplasmic translocation of β-catenin, de novo expression of vimentin), in 103 renal graft biopsy samples taken for routine surveillance or for a clinical indication.
RESULTS: We observed the nuclear accumulation of snail1 and phospho-smad2/3 in tubular cells displaying EMT. The level of snail1 was significantly correlated with the scores of EMT markers (β-catenin: ρ = 0.94, P < 0.0001; vimentin: ρ = 0.93, P < 0.0001) and with deteriorated graft function and proteinuria at the time of biopsy. Furthermore, intense staining for both snail1 and vimentin in tubular cells (≥10% of tubules) was predictive of graft dysfunction 21 months post-biopsy, independently of the other known risk factor for long-term graft dysfunction. In contrast, in both normal and diseased graft, zeb1 expression was detected exclusively in the endothelial cells of glomeruli and peritubular capillaries.
CONCLUSION: This study suggests that snail1 is closely related to the fibrogenic, EMT-like response of the tubular epithelium in human renal grafts and predictive of graft function loss.
METHODS: We used immunohistochemistry to detect the presence of these EMT transcriptional regulators along with that of two validated EMT markers (intra-cytoplasmic translocation of β-catenin, de novo expression of vimentin), in 103 renal graft biopsy samples taken for routine surveillance or for a clinical indication.
RESULTS: We observed the nuclear accumulation of snail1 and phospho-smad2/3 in tubular cells displaying EMT. The level of snail1 was significantly correlated with the scores of EMT markers (β-catenin: ρ = 0.94, P < 0.0001; vimentin: ρ = 0.93, P < 0.0001) and with deteriorated graft function and proteinuria at the time of biopsy. Furthermore, intense staining for both snail1 and vimentin in tubular cells (≥10% of tubules) was predictive of graft dysfunction 21 months post-biopsy, independently of the other known risk factor for long-term graft dysfunction. In contrast, in both normal and diseased graft, zeb1 expression was detected exclusively in the endothelial cells of glomeruli and peritubular capillaries.
CONCLUSION: This study suggests that snail1 is closely related to the fibrogenic, EMT-like response of the tubular epithelium in human renal grafts and predictive of graft function loss.