4.7 Article

Emerging functions of the nuclear receptor LRH-1 in liver physiology and pathology

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ELSEVIER
DOI: 10.1016/j.bbadis.2021.166145

Keywords

NR5A2; Hepatocytes; NAFLD; NASH; HCC

Funding

  1. Ecole Polytechnique Federale de Lausanne (EPFL), Switzerland
  2. Swiss National Science Foundation (SNSF), Switzerland [31003A_166695]
  3. China Scholarship Council, China
  4. Marie Sklodowska-Curie fellowship (EU H2020), Europe
  5. Swiss National Science Foundation (SNF) [31003A_166695] Funding Source: Swiss National Science Foundation (SNF)

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Liver receptor homolog-1 (LRH-1) plays crucial roles in the liver, not only regulating bile acid and cholesterol homeostasis but also coordinating various other hepatic metabolic processes. Recent advances have highlighted LRH-1 as an attractive target for treating non-alcoholic fatty liver disease and hepatocellular carcinoma.
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 liverassociated diseases, such as non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC).

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