The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology

Biochim Biophys Acta Mol Basis Dis. 2021 May 1;1867(5):166085. doi: 10.1016/j.bbadis.2021.166085. Epub 2021 Jan 24.

Abstract

Activated by retinoids, metabolites of vitamin A, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs) play important roles in a wide variety of biological processes, including embryo development, homeostasis, cell proliferation, differentiation and death. In this review, we summarized the functional roles of nuclear receptor RAR/RXR heterodimers in liver physiology. Specifically, RAR/RXR modulate the synthesis and metabolism of lipids and bile acids in hepatocytes, regulate cholesterol transport in macrophages, and repress fibrogenesis in hepatic stellate cells. We have also listed the specific genes that carry these functions and how RAR/RXR regulate their expression in liver cells, providing a mechanistic view of their roles in liver physiology. Meanwhile, we pointed out many questions regarding the detailed signaling of RAR/RXR in regulating the expression of liver genes, and hope future studies will address these issues.

Keywords: Bile acid hemostasis; Gene regulation; Lipid metabolism; Liver fibrogenesis; Liver physiology; Nuclear receptors; Retinoic acid receptors; Retinoid X receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation*
  • Humans
  • Liver / cytology
  • Liver / metabolism
  • Liver / physiology*
  • Protein Multimerization
  • Receptors, Retinoic Acid / chemistry
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism*
  • Retinoid X Receptors / chemistry
  • Retinoid X Receptors / genetics
  • Retinoid X Receptors / metabolism*
  • Signal Transduction

Substances

  • Receptors, Retinoic Acid
  • Retinoid X Receptors