Abstract
Podocytes injury is a major biomarker of primary glomerular disease that leads to massive proteinuria and kidney failure. The increased production of chemokine Fractalkine (FKN, CX3CL1) implicated as a hallmark in multiple inflammatory disease. However, the underlying mechanism of FKN on podocytes injury remains unknown. Here, we studied the effects of FKN in LPS-induced acute kidney injury (AKI) in wild type (WT) and FKN knockout (FKN-KO) mice. LPS stimulation resulted in kidney damage, increased expression of Bcl-2 family apoptosis protein while decreased the podocytes marker protein (nephrin and podocin) abundance compared with the control. LPS-induced FKN-KO mice exhibited reduced lethality and attenuated inflammatory cells infiltration, podocytes apoptosis and PI3K/Akt signal pathway inhibition compared with WT mice. Depletion of FKN served a protective effect in LPS-induced AKI by activating the PI3K/Akt signal pathway. In cultured podocytes, the interaction between FKN and PI3K/Akt signal pathway is well confirmed. FKN knockdown reduced podocytes apoptosis by regulating the Bcl-2 family, while this protective effect was reversed by co-administration of PI3K/Akt inhibitor (LY294002). These studies reveal a novel mechanistic property of FKN, PI3K/Akt signal and podocytes apoptosis.
Osthole protects sepsis-induced acute kidney injury via down-regulating NF-κB signal pathway