Rejection is the principal complication of kidney transplantation “Solez K – 2008 “ Injury to tubular epithelial cells (TEC) could contribute to fibrogenesis during late deterioration in kidney transplants, through the processes of epithelial to mesenchymal transition (EMT). “Vongwiwatana A – 2005 “. Endothelial to Mesenchymal Transition (EndMT) is a pathogenic process recently described in the progression of chronic renal damage. “Potenta S. – 2008  (full text)“. Tubular cells represent a significant source of IL-17 in ABMR and this event might be mediated by the complement system activation featuring this condition. “Loverre A – 2011 “. Aim of the study was to evaluate the role of IL-17 and Complement System in the induction of EMT and EndMT in acute and chronic rejection.
Materials and Methods
IL-17, E-cadherin, CD31, FSP1 and alpha-SMA protein expression were investigated by confocal analysis in graft biopsies with:
ATMR AcuteT-cell-Mediated Rejection (n=10)
ABMR Acute AntiBody-Mediated Rejection (n=10)
CTMR Chronic T-cell-Mediated Rejection (n=10)
CAHR Chronic Active Humoral Rejection (n=10)
The data were validate in endothelial cells (EndC) stimulated for 24h with IL-17 20 ng/ml and C3a 5×10-7M.
CAHR and ABMR were characterized by a significant increase in tubular IL-17 protein expression compared to CTMR and ATMR groups (Figura 1). Interestingly, CAHR and ABMR were characterized by a significant increase of tubular E-cadherin+/FSP1+ cells (Figura 2) and an increase of tubular E-cadherin+/alphaSMA+ cells in CAHR compared to ABMR (Figura 3) indicating the presence of EMT. Moreover, a significant increase of CD31+/FSP1+ cells in peritubular capillaries (Figura 4),and an increase of CD31+/alphaSMA+ cells in CAHR compared to ABMR (Figura 5) suggested the occurrence of EndMT. The number of FSP1+ cells correlated with IL-17 expression in ABMR and CAHR (R2 =0.41). Finally, in vitro we observed a significant increase of FSP1+ cells in EndC stimulated for 24h (Figura 6).
Our data suggest a synergic role of IL-17 and Complement in the induction of EMT and EndMT in CAHR and ABMR. Therapeutic inhibition of these systems may be essential to prevent the progression of renal damage.
The authors have no conflicts of interest to disclose.