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Downregulation of ubiquitous microRNA-320 in hepatocytes triggers RFX1-mediated FGF1 suppression to accelerate MASH progression

文献类型：期刊论文

作者Yang, Liu1,2; Li, Wenjun3; Chen, Yingfen1,2; Ya, Ru1,2; Qian, Shengying1,2; Liu, Li3; Hao, Yawen1,2; Zai, Qiuhong1,2; Xiao, Peng4; Hwang, Seonghwan5,6
刊名ACTA PHARMACEUTICA SINICA B
出版日期2025-08-01
卷号15期号:8页码:4096-4114
关键词miR-320 MASLD RFX1 FGF1 AMPK
ISSN号2211-3835
DOI10.1016/j.apsb.2025.06.007
英文摘要Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 in situ hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of Rfx1 in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression. (c) 2025 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
WOS关键词FATTY LIVER-DISEASE ; TRANSCRIPTION ; METABOLISM ; FIBROBLAST-GROWTH-FACTOR-1 ; STEATOHEPATITIS ; NASH
资助项目National Natural Science Foundation of China[82300657] ; National Natural Science Foundation of China[82270601] ; National Key Research and Development Program of China[2023YFA1800804] ; Natural Science Foundation of Shanghai[22ZR1473800]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001562025100010
出版者INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
源URL[http://119.78.100.183/handle/2S10ELR8/321387]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者He, Yong
作者单位1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med SIMM, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
4.Jilin Univ, First Hosp Jilin Univ, Dept Hepatol, Changchun 130021, Peoples R China
5.Pusan Natl Univ, Coll Pharm, Busan 46241, South Korea
6.Pusan Natl Univ, Res Inst Drug Dev, Busan 46241, South Korea
推荐引用方式
GB/T 7714		 Yang, Liu,Li, Wenjun,Chen, Yingfen,et al. Downregulation of ubiquitous microRNA-320 in hepatocytes triggers RFX1-mediated FGF1 suppression to accelerate MASH progression[J]. ACTA PHARMACEUTICA SINICA B,2025,15(8):4096-4114.
APA Yang, Liu.,Li, Wenjun.,Chen, Yingfen.,Ya, Ru.,Qian, Shengying.,...&He, Yong.(2025).Downregulation of ubiquitous microRNA-320 in hepatocytes triggers RFX1-mediated FGF1 suppression to accelerate MASH progression.ACTA PHARMACEUTICA SINICA B,15(8),4096-4114.
MLA Yang, Liu,et al."Downregulation of ubiquitous microRNA-320 in hepatocytes triggers RFX1-mediated FGF1 suppression to accelerate MASH progression".ACTA PHARMACEUTICA SINICA B 15.8(2025):4096-4114.

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来源：上海药物研究所

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