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 are activated hepatic stellate cells. Different NRs 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.

核受体是配体激活的转录因子，可调节参与肝纤维化的多种关键分子信号的基因表达。肝纤维化的主要细胞驱动因素是活化的肝星状细胞。不同的 NRs 调节促炎和促纤维化细胞因子的肝脏表达，促进肝星状细胞向纤维化肌成纤维细胞的转化。重要的是，核受体调节促进肝纤维化和/或允许肝纤维化消退的基因表达回路。在这篇综述中，我们强调了核受体对肝纤维化的直接和间接影响，重点是肝星状细胞，并讨论了核受体调节在抗纤维化和抗炎作用方面的潜在治疗效果。