Background: The epithelial response to injury is stereotyped, and is reminiscent of an epithelial-to-mesenchymal transition (EMT), such as observed during embryogenesis and tumorigenesis. In the context of solid organ transplantation, the acquisition of EMT-like features by epithelial cells is frequent, and predictive of graft fibrogenesis. Here, we studied the possible involvement of several major transcriptional regulators, such as snail1, phospho-Smad 2/3 and zeb1, for EMT induction in human renal grafts.

Methods: We used immuno-histochemistry to detect the expression of these EMT transcriptional regulators along with two validated EMT markers (intracytoplasmic translocation of beta-catenin, de novo expression of vimentin), in a 103 kidney biopsy samples taken for renal graft surveillance or for a cause.

Results: First, we observed a nuclear accumulation of snail1 and phospho-smad2/3 in tubules displaying EMT. The level of snail1 expression was significantly correlated with EMT markers (Β catenin: r=0.942, p<0.0001; vimentin: r=0.93, p<0.0001), and with deteriorated graft function and proteinuria at the time of biopsy. Furthermore, an intense (≥10% of tubules) expression of stain for both snail1 and vimentin in tubular cells was predictive of a graft dysfunction at 21 months post-biopsy independent of other known risk factors for long term graft dysfunction. In contrast, zeb1 expression was exclusively detected in the endothelial cells of glomeruli and peritubular capillaries, in normal as in diseased kidneys.

Conclusion: This study suggests that snail1 is closely related to the fibrogenic, EMT-like response of the tubular epithelium in human renal grafts.

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