School of Public Health, the key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou 550025, China.
Guizhou Provincial Center for Disease Control and Prevention, Guiyang, Guizhou 550004, China.
Int Immunopharmacol. 2021 Oct;99:107938. doi: 10.1016/j.intimp.2021.107938. Epub 2021 Aug 6.
The liver is not only the main metabolic site of exogenous compounds and drugs, but also an important immune organ in the human body. When a large number of nonself substances (such as drugs, alcohol, pathogens, microorganisms and their metabolites) enter the liver, they will cause serious liver diseases, including liver fibrosis, liver cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Macrophages are the first line of defense against the invasion of exogenous pathogens and significant cellular components of the innate immune system. Macrophages have strong heterogeneity and plasticity. When different pathogens invade the body, they cause different types of polarization of macrophages through different molecular mechanisms. Notch signaling is considered to be the key regulator of the biological function of macrophages. Activating Notch signaling can regulate the differentiation of macrophages into M1 and play a role in promoting inflammation and antitumor activity, while blocking Notch signaling can polarize macrophages to M2, suppressing inflammation and promoting tumor growth. However, there are few studies on regulation of macrophage polarization by the Notch signaling pathway in liver diseases. Therefore, in this review, we will introduce the role of the Notch signaling pathway in regulating macrophage polarization in liver diseases.
肝脏不仅是外源化合物和药物的主要代谢部位,也是人体的一个重要免疫器官。当大量非自身物质(如药物、酒精、病原体、微生物及其代谢物)进入肝脏时,会导致严重的肝脏疾病,包括肝纤维化、肝硬化、肝功能衰竭和肝细胞癌(HCC)。巨噬细胞是抵御外源性病原体入侵的第一道防线,也是先天免疫系统的重要细胞成分。巨噬细胞具有很强的异质性和可塑性。当不同的病原体侵入人体时,它们通过不同的分子机制引起巨噬细胞的不同类型极化。Notch 信号被认为是巨噬细胞生物学功能的关键调节因子。激活 Notch 信号可以调节巨噬细胞向 M1 的分化,并发挥促进炎症和抗肿瘤活性的作用,而阻断 Notch 信号可以使巨噬细胞向 M2 极化,抑制炎症并促进肿瘤生长。然而,关于 Notch 信号通路在肝脏疾病中调节巨噬细胞极化的研究较少。因此,在本综述中,我们将介绍 Notch 信号通路在调节肝脏疾病中巨噬细胞极化的作用。