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AhR-STAT3-HO-1/COX-2 signalling pathway may restrict ferroptosis and improve hMSC accumulation and efficacy in mouse liver

文献类型：期刊论文

作者Han, Li6,7; Ma, Chenhui5,7; Wu, Zhitao4,7; Xu, Huiming3; Li, Hai2; Pan, Guoyu1,6,7
刊名BRITISH JOURNAL OF PHARMACOLOGY
出版日期2023-09-14
页码17
ISSN号0007-1188
关键词aryl hydrocarbon receptor ferroptosis iron ischaemia/reperfusion liver injury liver disease mesenchymal stem cells
DOI10.1111/bph.16208
通讯作者Pan, Guoyu(gypan@simm.ac.cn)
英文摘要Background and Purpose: The low efficacy of mesenchymal stem cells (MSCs) has restricted their application in the treatment of liver disease. Emerging evidence suggested that ferroptosis may provoke hepatocyte dysfunction and exacerbate damage to the liver microenvironment. Here, we have investigated the contribution of liver ferroptosis to the elimination and effectiveness of human MSC (hMSC). Furthermore, potential links between liver ferroptosis and aryl hydrocarbon receptors (AhR) were explored.Experimental Approach: Two mouse models, iron supplement-induced hepatic ferroptosis and hepatic ischaemia/reperfusion (I/R) injury, were used to identify effects of ferroptosis on hMSC pharmacokinetics (PK)/pharmacodynamics (PD).Key Results: AhR inhibition attenuated hepatic ferroptosis and improved survival of hMSCs. hMSC viability was decreased by iron supplementation or serum from I/R mice. The AhR antagonist CH223191 reversed iron overload and oxidative stress induced by ferroptosis and increased hMSC concentration and efficacy in mouse models. Effects of CH223191 were greater than those of deferoxamine, a conventional ferroptosis inhibitor. Transcriptomic results suggested that the AhR-signal transducer and activator of transcription 3 (STAT3)-haem oxygenase 1/COX-2 signalling pathway is critical to this process. These results were confirmed in a mouse model of hepatic I/R injury. In mice pre-treated with CH223191, hMSC exhibited more potent protective effects, linked to decreased hepatic ferroptosis.Conclusion and Implications: Our findings showed that ferroptosis was a critical factor in determining the fate of hMSCs. Inhibition of AhR decreased hepatic ferroptosis, thereby increasing survival and therapeutic effects of hMSCs in mouse models of liver disease. image
WOS关键词ARYL-HYDROCARBON RECEPTOR ; MESENCHYMAL STEM-CELLS ; HEART FUNCTION ; CONCISE GUIDE ; STROMAL CELLS ; THERAPY ; PHYSIOLOGY
资助项目National Natural Science Foundation of China[81872927] ; Chinese Academy of Sciences[XDA16020205]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者WILEY
WOS记录号WOS:001066637800001
源URL[http://119.78.100.183/handle/2S10ELR8/307173]  
专题中国科学院上海药物研究所
通讯作者Pan, Guoyu
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China
2.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Gastroenterol, Shanghai, Peoples R China
3.Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Renji MedX Clin Stem Cell Res Ctr, Renji Hosp,Sch Med, Shanghai, Peoples R China
4.Nanjing Univ Chinese Med, Nanjing, Peoples R China
5.Univ Nottingham Ningbo China, Dept Chem & Environm Engn, Ningbo, Peoples R China
6.Univ Chinese Acad Sci, Beijing, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Han, Li,Ma, Chenhui,Wu, Zhitao,et al. AhR-STAT3-HO-1/COX-2 signalling pathway may restrict ferroptosis and improve hMSC accumulation and efficacy in mouse liver[J]. BRITISH JOURNAL OF PHARMACOLOGY,2023:17.
APA Han, Li,Ma, Chenhui,Wu, Zhitao,Xu, Huiming,Li, Hai,&Pan, Guoyu.(2023).AhR-STAT3-HO-1/COX-2 signalling pathway may restrict ferroptosis and improve hMSC accumulation and efficacy in mouse liver.BRITISH JOURNAL OF PHARMACOLOGY,17.
MLA Han, Li,et al."AhR-STAT3-HO-1/COX-2 signalling pathway may restrict ferroptosis and improve hMSC accumulation and efficacy in mouse liver".BRITISH JOURNAL OF PHARMACOLOGY (2023):17.

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来源：上海药物研究所

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