The role and mechanism of SDF-1/CXCR4 signaling pathway in rat model of chronic renal allograft rejection

Abstract

Objective To investigate the role and mechanism of SDF-1/CXCR4 in the development of chronic rejection (CR) in rat models. Methods CR rat models were established using Fisher 344 to Lewis rats.In the blank control group (n=10), Lewis rats getting isotransplantation were treated with Cyclosporine A. CR rat models were established in positive group (n=10) and the rats were treated with Cyclosporine A. CR rat models were also established in CXCR4 antagonism group (n=10) and the rats were treated with both Cyclosporine A and AMD3100 (1 mg/kg). The serum creatinine levels were monitored every week.Kidney grafts were harvested 12 weeks after transplantation for histological analysis.We evaluated graft injuries using chronic allograft damage index (CADI) scores.Q-PCR and Western blotting were used to measure CXCR4, TGF-β1/Smad3 signaling pathway and α-smooth muscle actin (α-SMA) expression in renal allograft tissues. Results The serum creatinine levels in blank control group and CXCR4 antagonism group were significantly lower than those in positive control group (P<0.05). The blank control group and CXCR4 antagonism group presented milder pathological manifestations of CR.The CADI score in CXCR4 antagonism group was 3.54, which was lower than that of positive control group (P<0.05). The expression of biological markers in TGF-β1/Smad3 signaling pathway and SDF-1/CXCR4 signaling pathway was significantly lower in blank control group and CXCR4 antagonism group than in positive control group (P<0.05). Conclusion SDF-1/CXCR4 signaling pathway may play a crucial role in the development of CR.The usage of SDF-1/CXCR4 antagonist can protect renal allograft by inhibiting the TGF-β1/Smad3 pathway.Therefore, antagonism of CXCR4 may provide a novel way to prevent the development of CR. Key words: Graft rejection, chronic; Receptors, chemokine; Kidney transplantation; Rats