BACKGROUND

Podocyte injury is a major biomarker of primary glomerular disease, which leads to massive proteinuria and kidney failure. The increased production of the chemokine, fractalkine (FKN, CX3CL1), is a hallmark of multiple inflammatory diseases. However, the underlying mechanism of FKN in podocyte injury remains unknown.

METHODS

In this study, we performed an LPS infusion model in FKN knockout (FKN, FKN-KO) mice. In cultured podocytes, we used plasmids to knockdown FKN and treated the podocytes with PI3K/Akt inhibitor (LY294002). Haematoxylin and eosin (HE) staining, Western Bolt, Co-immunoprecipitation (Co-IP), Immunofluorescence staining and flow cytometric analysis were employed to establish the role of FKN in podocyte injury.

RESULTS

LPS stimulation resulted in kidney damage, increased the expression of the Bcl-2 family apoptosis protein, and decreased podocyte marker protein (nephrin, podocin and WT1) abundance compared with the WT mice. LPS-induced FKN-KO mice exhibited reduced lethality and inflammatory cell infiltration, podocyte apoptosis, and PI3K/Akt signal pathway inhibition compared to WT mice. In cultured podocytes, the interaction between FKN and the PI3K/Akt signalling pathway was well confirmed. FKN knockdown reduced podocyte apoptosis by regulating the Bcl-2 family; however, this protective effect was reversed by the co-administration of a PI3K/Akt inhibitor (LY294002).

CONCLUSION

Overall, these findings reveal a novel mechanistic property of FKN, PI3K/Akt signalling, and podocyte apoptosis.