期刊
MEDICAL HYPOTHESES
卷 146, 期 -, 页码 -出版社
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.mehy.2020.110379
关键词
Denosumab; Fibrosis; Metabolic (dysfunction)-associated fatty liver disease; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Receptor activator of nuclear factor kappa-B ligand; Osteoprotegerin
NAFLD is a highly prevalent liver disease without any approved treatment. This study explores the potential association between hepatic RANKL upregulation and the pathogenesis of NAFLD, suggesting denosumab as a potential candidate for NASH in drug-repurposing studies.
Background: Nonalcoholic fatty liver disease (NAFLD) is a disease of high prevalence without any approved treatment. Nonalcoholic steatohepatitis (NASH) is an advanced phenotype of the disease and the main focus of ongoing clinical trials. Denosumab, a human monoclonal antibody, which binds and inhibits the receptor activator of nuclear factor kappa-B ligand (RANKL), is a licensed medication for postmenopausal, male and glucocorticoid-induced osteoporosis, as well as for metastatic bone disease associated with specific cancers. Hepatic RANKL upregulation has been shown in a transgenic mice model. Hypothesis: We hypothesized that hepatic RANKL upregulation may be associated with hepatic steatosis and inflammation, thus playing a role in the pathogenesis of NAFLD. Conclusion: If this hypothesis is verified, denosumab, an established anti-osteoporotic medication, may be considered as a candidate for NASH in drug-repurposing studies.
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