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This study was designed to explore whether aquaporin 1(AQP1), P53 and P21 can be used as diagnostic biomarkers of lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and potential indicators of sepsis-induced multiple organ injury. Bioinformatics results demonstrated that AQP1, P53, P21 was dramatically elevated 6h after Cecal ligation and puncture (CLP)-AKI in rat renal tissue. The expression of AQP1, P53, P21, NGAL and KIM-1 in kidney were increased significantly at first and then decreased gradually in LPS-induced AKI rats. Histopathological sections showed swelling of tubular epithelial cells and destruction of basic structures as well as infiltration of numerous inflammatory cells in LPS-induced AKI. Moreover, the expressions of AQP1, P53 and P21 in heart were significantly increased in LPS treatment rats, while the AQP1 expressions in lung and small intestine were significantly decreased. The level of NGAL mRNA in heart, lung and small intestine was firstly increased and then decreased during LPS treatment rats, but the expression of KIM-1 mRNA was not affected. Therefore, our results suggest that AQP1, P53 and P21 is remarkably upregulated in LPS-induced AKI, which may be considered as a potential novel diagnostic biomarker of Septic AKI. NGAL may serve as a biomarker of sepsis-induced multiple organ damage during the process of LPS-induced AKI. [ABSTRACT FROM AUTHOR]