Targeting AhR suppresses hepatocyte ferroptosis in MASH by regulating the Pten/Akt/β catenin axis
文献类型：期刊论文
| 作者 | Ma, Chenhui3,4,5; Han, Li3,4; Zhao, Wenxuan2,3,4; Chen, Feihong3,4; Huang, Ruimin2,3,4 ; Pang, Cheng Heng5; Zhu, Zheying1; Pan, Guoyu2,3,4
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| 刊名 | BIOCHEMICAL PHARMACOLOGY
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| 出版日期 | 2025-02-01 |
| 卷号 | 232页码:13 |
| 关键词 | Metabolic dysfunction-associated steatohepati- tis Liver disease Iron Ferroptosis Aryl hydrocarbon Receptor Pten beta-catenin |
| ISSN号 | 0006-2952 |
| DOI | 10.1016/j.bcp.2024.116711 |
| 通讯作者 | Huang, Ruimin(rmhuang@simm.ac.cn) ; Pang, Cheng Heng(chengheng.pang@nottingham.edu.cn) ; Zhu, Zheying(Zheying.Zhu@nottingham.ac.uk) ; Pan, Guoyu(gypan@simm.ac.cn) |
| 英文摘要 | Aryl hydrocarbon Receptor (AhR), an essential host regulator, has been observed to be significantly upregulated in patients with Metabolic dysfunction-associated steatohepatitis (MASH). However, the underlying mechanism remains unclear. The specific AhR antagonist CH223191 and siRNAs were employed to investigated the role of AhR and its potential as a therapeutic target for MASH in mice and hepatocytes model. Significant upregulation of hepatic AhR was found in our MASH model and across three public datasets. CH223191 (5 mg/kg) treatment effectively ameliorated lipid deposition, serum ALT/AST level, inflammatory cytokines and hepatocyte senescence. Moreover, inhibiting AhR reduced aberrant iron overload, MDA and ROS levels, and suppressed iron transporter DMT1 and iron storage protein ferritin. Furthermore, CH223191 treatment resulted in the restoration of (3-catenin and Pten while reducing the phosphorylation of Akt. Suppression of Pten or (3-catenin by specific antagonists significantly abolished the hepatoprotective effects of CH223191, leading to increased DMT1 and ferritin and subsequent hepatic ferroptosis in mice. In conclusions, these findings suggested a novel regulatory role of AhR plays in ferroptosis and iron overload through the Pten/Akt/(3catenin pathway, which makes AhR a promising therapeutic target for the treatment of MASH. |
| WOS关键词 | ACTIVATION |
| 资助项目 | National Science Foundation of China[81872927] ; Organ Reconstruction and Manufacturing Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16020205] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001392185000001 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315630]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Huang, Ruimin; Pang, Cheng Heng; Zhu, Zheying; Pan, Guoyu |
| 作者单位 | 1.Univ Nottingham, Sch Pharm, Div Mol Therapeut & Formulat, Univ Pk Campus, Nottingham NG7 2RD, England 2.Nanjing Univ Chinese Med, Nanjing 210029, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 5.Univ Nottingham Ningbo China, Dept Chem & Environm Engn, Ningbo 315100, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ma, Chenhui,Han, Li,Zhao, Wenxuan,et al. Targeting AhR suppresses hepatocyte ferroptosis in MASH by regulating the Pten/Akt/β catenin axis[J]. BIOCHEMICAL PHARMACOLOGY,2025,232:13. |
| APA | Ma, Chenhui.,Han, Li.,Zhao, Wenxuan.,Chen, Feihong.,Huang, Ruimin.,...&Pan, Guoyu.(2025).Targeting AhR suppresses hepatocyte ferroptosis in MASH by regulating the Pten/Akt/β catenin axis.BIOCHEMICAL PHARMACOLOGY,232,13. |
| MLA | Ma, Chenhui,et al."Targeting AhR suppresses hepatocyte ferroptosis in MASH by regulating the Pten/Akt/β catenin axis".BIOCHEMICAL PHARMACOLOGY 232(2025):13. |
入库方式： OAI收割
来源：上海药物研究所
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