Aurora kinase A regulates liver regeneration through macrophages polarization and Wnt/β-catenin signalling

Background and Aims Liver regeneration is a complex process regulated by a variety of cells, cytokines and biological pathways. Aurora kinase A (AURKA) is a serine/threonine kinase that plays a role in centrosome maturation and spindle formation during the cell division cycle. The purpose of this study was to further explore the mechanism of AURKA on liver regeneration and to identify new possible targets for liver regeneration. Methods The effect and mechanism of AURKA on liver regeneration were studied using a 70% hepatectomy model. Human liver organoids were used as an in vitro model to investigate the effect of AURKA on hepatocyte proliferation. Results AURKA inhibition significantly reduced the level of beta-catenin protein by reducing the phosphorylation level of glycogen synthase kinase-3 beta (GSK-3 beta), leading to the inhibition of liver regeneration. Further studies showed that AURKA co-localized and interacted with GSK-3 beta in the cytoplasm of hepatocytes. When phosphorylation of GSK-3 beta was enhanced, the total GSK-3 beta level remained unchanged, while AURKA was not affected, and beta-catenin protein levels were increased. In addition, AURKA inhibition affected the formation and proliferation of human liver organoids. Furthermore, AURKA inhibition led to the polarization of M1 macrophages and the release of interleukin-6 and Tumour necrosis factor alpha, which also led to reduced liver regeneration and increased liver injury. Conclusions These results provide more details on the mechanism of liver regeneration and suggest that AURKA is an important regulator of this mechanism.

Automated summary

This study investigated the mechanism of AURKA on liver regeneration using a 70% hepatectomy model and human liver organoids. The results showed that AURKA inhibition reduced beta-catenin levels by decreasing GSK-3 beta phosphorylation, leading to impaired liver regeneration. Additionally, AURKA inhibition affected human liver organoid formation, M1 macrophage polarization, and cytokine release, ultimately exacerbating liver injury.