Nuclear receptors in liver fibrosis

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1867

Article

Koenigshofer, Philipp^1,2,3  Brusilovskaya, Ksenia^1,2,3  Petrenko, Oleksandr^1,2,3,4,5  Hofer, Benedikt Silvester^1,2,3  Schwabl, Philipp^1,2,3  Trauner, Michael¹  Reiberger, Thomas^1,2,3,4,5 

[1] Med Univ Vienna, Dept Med 3, Div Gastroenterol & Hepatol, Vienna, Austria

[2] Med Univ Vienna, Vienna Expt Hepat Hemodynam Lab HEPEX, Vienna, Austria

[3] Med Univ Vienna, Christian Doppler Lab Portal Hypertens & Liver Fi, Vienna, Austria

[4] Ludwig Boltzmann Inst Rare & Undiagnosed Dis, Vienna, Austria

[5] Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria

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

DOI  :  10.1016/j.bbadis.2021.166235

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free