Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Biochim Biophys Acta Mol Basis Dis. 2021 Aug 1;1867(8):166145. doi: 10.1016/j.bbadis.2021.166145. Epub 2021 Apr 20.
Nuclear receptors play pleiotropic roles in cell differentiation, development, proliferation, and metabolic processes to govern liver physiology and pathology. The nuclear receptor, liver receptor homolog-1 (LRH-1, NR5A2), originally identified in the liver as a regulator of bile acid and cholesterol homeostasis, was recently recognized to coordinate a multitude of other hepatic metabolic processes, including glucose and lipid processing, methyl group sensing, and cellular stress responses. In this review, we summarize the physiological and pathophysiological functions of LRH-1 in the liver, as well as the molecular mechanisms underlying these processes. This review also focuses on the recent advances highlighting LRH-1 as an attractive target for liver-associated diseases, such as non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC).
核受体在细胞分化、发育、增殖和代谢过程中发挥多效性作用,以调节肝脏的生理和病理。核受体肝受体同源物-1(LRH-1,NR5A2)最初在肝脏中被鉴定为胆汁酸和胆固醇稳态的调节剂,最近被认为协调多种其他肝脏代谢过程,包括葡萄糖和脂质处理、甲基组感应和细胞应激反应。在这篇综述中,我们总结了 LRH-1 在肝脏中的生理和病理生理学功能,以及这些过程的分子机制。这篇综述还重点介绍了最近的进展,强调了 LRH-1 作为与肝脏相关疾病(如非酒精性脂肪性肝病(NAFLD)和肝细胞癌(HCC))的有吸引力的治疗靶点。