4.7 Article

Nuclear receptors in liver fibrosis

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ELSEVIER
DOI: 10.1016/j.bbadis.2021.166235

Keywords

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

Funding

  1. Federal Ministry for Digital and Economic Affairs
  2. Christian Doppler Research Association
  3. Boehringer Ingelheim
  4. Medical Scientific Fund of the Mayor of the City of Vienna [18070]

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Nuclear receptors play a crucial role in regulating gene expression involved in liver fibrosis, especially in hepatic stellate cells. Further research on nuclear receptors-related signaling may lead to the development of effective anti-fibrotic therapies for patients with liver disease.
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.

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