Vascular rarefaction is critical in the development of renal fibrosis. Pericytes regulate renal blood flow and might be an important source of renal interstitial myofibroblasts; however little is known on their possible involvement in I/R injury.

Ten pigs underwent to 30min of renal warm I, followed by 24h of R. Five pigs were treated with C1-Inhibitor. Biopsies were analyzed by immunohistochemistry for PDGFRβ. Immunofluorescence(IF) was performed on human pericytes stimulated with C5a for 24h.

I/R injury led to pericyte-myofibroblast trans-differentiation as indicated by a significant reduction in PDGFRβ expression in peritubular capillaries (p<0.05). Pericyte trans-differentiation was associated by alpha-SMA induction, a marker of myofibroblasts without induction of apoptosis (Caspase-3-). Pericyte activation was accompanied by a significant decrease in peritubular capillary lumen area (p<0.05). Interestingly, Complement inhibition preserved PDGFRβ expression (p<0.05), limited alpha-SMA and restored basal capillary area fraction (p<0.05). In accordance, C5a significantly activated pericytes in vitro with down regulation of PDGFRβ (p<0.05), remodeling of αSMA indicating myofibroblasts trans-differentiation (TGF-beta, positive control).

Our study demonstrated that Complement caused pericytes-myofibroblasts trans-differentiation in renal I/R injury with reduction of peritubular capillary area. C1-Inh may be a possible therapeutic strategy to preserve I/R induced vascular rarefaction and myofibroblasts development in transplanted kidney.

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