CrmA gene transfer rescued CsA-induced renal cell apoptosis in graft kidney

Abstract

Cyclosporine A(CsA) causes significant nephrotoxicity that contribute to kidney graft loss in the long-term, it can induce cell apoptosis in renal cortex and medulla, reduce kidney function. The mechanisms are complex and involved in six apoptosis pathways including classical pathway, mitochondrial pathway, endoplasmic reticulum pathway, angiotensin II pathway, NO- and hypertonicity-related pathway. All these pathways may converge to a single way by activated Caspase-3, -6, -8, -9 and -12 that may become a potential new target for intervention. CrmA protein belonging to one of serine protease inhibitor family members, it widely inhibits the inflammatory Caspases and apoptotic Caspases and has a strong function on inhibiting apoptosis induced by many chemical inducers through effectively blocking Caspase-1, -3, -4, -5, -8, -9, and -10 enzymes. It is not reported if CrmA is resistant to apoptosis induced by immunosuppressant so far. Therefore we speculate CrmA can block down CsA-induced renal cell apoptosis through inhibiting the Caspase-3, -6, -8, -9 and -12 activated and further to eliminate CRD induced by CsA.