The Notch signaling pathway regulates macrophage polarization in liver diseases

Int Immunopharmacol. 2021 Oct:99:107938. doi: 10.1016/j.intimp.2021.107938. Epub 2021 Aug 6.

Abstract

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.

Keywords: Liver diseases; Macrophage polarization; Notch signaling pathway.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cytokines / metabolism
  • Endoplasmic Reticulum / metabolism
  • Humans
  • Inflammation / metabolism
  • Liver
  • Liver Diseases / metabolism*
  • Macrophage Activation
  • Macrophages / classification
  • Macrophages / metabolism*
  • Receptors, Notch / metabolism*
  • Signal Transduction

Substances

  • Cytokines
  • Receptors, Notch