Nuclear receptors in liver fibrosis

Biochim Biophys Acta Mol Basis Dis. 2021 Dec 1;1867(12):166235. doi: 10.1016/j.bbadis.2021.166235. Epub 2021 Jul 31.


Nuclear receptors are ligand-activated transcription factors that regulate gene expression of a variety of key molecular signals involved in liver fibrosis. The primary cellular driver of liver fibrogenesis is activated hepatic stellate cells. Different nuclear receptors regulate the hepatic expression of pro-inflammatory and pro-fibrogenic cytokines that promote the transformation of hepatic stellate cells into fibrogenic myofibroblasts. Importantly, nuclear receptors regulate gene expression circuits that promote hepatic fibrogenesis and/or allow liver fibrosis regression. In this review, we highlight the direct and indirect influence of nuclear receptors on liver fibrosis, with a focus on hepatic stellate cells, and discuss potential therapeutic effects of nuclear receptor modulation in regard to anti-fibrotic and anti-inflammatory effects. Further research on nuclear receptors-related signaling may lead to the clinical development of effective anti-fibrotic therapies for patients with liver disease.

Keywords: AR; ER; FXR; GR; LXR; Liver fibrosis; MR; Nuclear receptor; PPAR; RAR; RXR; THR; VDR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Gene Expression Regulation / genetics
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology
  • Humans
  • Ligands
  • Liver / metabolism*
  • Liver / pathology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / pathology
  • Myofibroblasts / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Signal Transduction / genetics
  • Transcription Factors / genetics


  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors