Autophagy deficiency promotes M1 macrophage polarization to exacerbate acute liver injury via ATG5 repression during aging

• DOI: 10.1038/s41420-021-00797-2
• Publication Date: 2021-12-20T10:03:30Z
• Authors: Rui Liu; Juanjuan Cui; Yating Sun; Wentao Xu; Ziming Wang; Miaomiao Wu; Huke Dong; Congcong Yang; Shaocheng Hong; Shi Yin; Hua Wang
• Keywords: Macrophage polarization

Abstract Aging disrupts the maintenance of liver homeostasis, which impairs hepatocyte regeneration and aggravates acute injury (ALI), ultimately leading to development failure (ALF), a systemic inflammatory response, even death. Macrophages influence progression outcome ALI through innate immune system. However, it is still unclear how macrophages regulate during aging. The variation in macrophage autophagy with aging on polarization cytokine release were assessed BMDMs vitro. Then, after subjected several treatments intravenously or intraperitoneally injected into mice, thioacetamide (TAA)-induced (TAA-ALI) was established, its effects inflammation, injury, mortality assessed. We found that aggravated along increases levels proinflammatory mediators, presenting senescence-associated secretory phenotype (SASP), promoted M1 phenotype. In addition, decreased significantly aged ascribed ATG5 repression Notably, enhancing restored observed under young conditions. Finally, restoration enhanced protective effect against TAA-ALI, similar M2 induced by IL-4. Overall, we demonstrated an important aggravating factor associated