期刊
PHARMACOLOGICAL RESEARCH
卷 195, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2023.106886
关键词
Liver fibrosis; Semaphorin 4D; Retinol metabolism; AOX1; Retinoic acid receptor alpha
Liver fibrosis, a common feature in chronic liver diseases, can be alleviated by knockout of Sema4D, which has been found to regulate retinol metabolism and the balance of specific immune cells.
Liver fibrosis can occur in many chronic liver diseases, and no effective treatments are available due to the poorly characterized molecular pathogenesis. Semaphorin 4D (Sema4D) has immune functions and serves important roles in T cell priming. Here, we found that Sema4D was highly expressed in fibrotic liver, and the expression of Sema4D increased with hepatic stellate cells (HSCs) activation. Knockout of Sema4D alleviated liver fibrosis. Mechanistically, knockout of Sema4D alleviated liver fibrosis by suppressing the expression of AOX1 in retinol metabolism. Further investigation demonstrated that retinoic acid receptor alpha (RARA), an important nuclear receptor of retinoic acid, was reduced by Sema4D knockout during liver fibrogenesis. Sema4D knockout-mediated suppression of liver fibrosis was partly mediated by regulating the balance of Th1, Th2, Th17, and T-bet(+)Treg cells via inhibiting AOX1/RARA. Thus, targeting Sema4D may hold promise as a potential therapeutic approach for treating liver fibrosis.
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