Fractalkine aggravates LPS-induced macrophage activation and acute kidney injury via Wnt/β-catenin signalling pathway

Fractalkine (CX3CL1, FKN), a CX3C gene sequence inflammatory chemokine, has been found to have pro-inflammatory and pro-adhesion effects. Macrophages are immune cells with a critical role in regulating the inflammatory response. The imbalance of M1/M2 macrophage polarization can lead to aggravated inflammation. This study attempts to investigate the mechanisms through which FKN regulates macrophage activation and the acute kidney injury (AKI) involved in inflammatory response induced by lipopolysaccharide (LPS) by using FKN knockout (FKN-KO) mice and cultured macrophages. It was found that FKN and Wnt/beta-catenin signalling have a positive interaction in macrophages. FKN overexpression inhibited LPS-induced macrophage apoptosis. However, it enhanced their cell viability and transformed them into the M2 type. The effects of FKN overexpression were accelerated by activation of Wnt/beta catenin signalling. In the in vivo experiments, FKN deficiency suppressed macrophage activation and reduced AKI induced by LPS. Inhibition of Wnt/beta-catenin signalling and FKN deficiency further mitigated the pathologic process of AKI. In summary, we provide a novel mechanism underlying activation of macrophages in LPS-induced AKI. Although LPS-induced murine AKI was unable to completely recapitulate human AKI, the positive interactions between FKN and Wnt/beta-catenin signalling pathway may be a therapeutic target in the treatment of kidney injury.

Automated summary

Fractalkine (FKN) interacts positively with Wnt/beta-catenin signaling in macrophages, playing a crucial role in LPS-induced acute kidney injury (AKI). FKN overexpression can attenuate LPS-induced macrophage apoptosis and promote their transformation into the beneficial M2 type, suggesting a potential therapeutic target for kidney injury.