The Effect Of Apoptosis Stimulating Protein Two Of P53 On Acute Kidney Injury Through The Regulation Of Autophagy

Objective:To explore the role of apoptosis stimulating protein two of p53?ASPP2?in acute kidney injury?AKI?induced by ischemia reperfusion in mice.Methods:To establish an AKI mouse model induced by ischemia reperfusion?I/R?in wild-type(ASPP2^+/+)mice and ASPP2 haploinsufficient(ASPP2^+/-)mice.The expression profile of ASPP2 was examined in ASPP2^+/+mice.The renal function,inflammatory cytokines,the degree of renal tissue damage and cellular apoptosis were assessed in ASPP2^+/+and ASPP2^+/-mice,and the expression of autophagy-related proteins were also detected in these mice.Then,using autophagy inhibitor 3-methyladenine?3-MA?to inhibit autophagy.Changes in renal function and renal tissue damage were analyzed in ASPP2^+/+and ASPP2^+/-mice treated with 3-MA or vehicle.Results:The expression profile of ASPP2 was up-regulated at the early stage and down-regulated at the late stage during renal ischemia reperfusion injury.Compared with ASPP2^+/+mice,the damage of ASPP2^+/-mice was much lighter after undergoing renal injury,which mainly exhibited in less histologic changes of tubular dilation,loss of brush borders,tubular cells necrosis and tubular cells swelling.And the biochemical indicators showed lower levels of serum creatinine?Scr?and blood urea nitrogen?BUN?,and less apoptosis as well as inflammatory response.In addition,ASPP2 deficiency enhanced autophagic activity,which was reflected in the increase of the conversion of LC3-II,the expression of autophagy related genes such as Atg7,Atg5 and Beclin-1,and the degradation of p62.Compared with mice not treated with 3-MA,the inhibition of autophagy can aggravate acute kidney injury induced by ischemia reperfusion in ASPP2^+/-mice,as evidenced by the elevated levels of Scr and BUN,the severer degree of histological damage,and the increase of inflammatory cytokines expression and cellular apoptosis.Consequently,the inhibition of autophagy reversed the protective effect of ASPP2 on acute kidney injury.Conclusion:In the mice model of renal ischemia reperfusion injury,ASPP2 deficiency can ameliorate acute kidney injury induced by ischemia reperfusion via attenuating cellular inflammatory response and cellular apoptosis,which was depended on the activation of autophagy.