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Human-Induced Hepatocytes-Derived Extracellular Vesicles Ameliorated Liver Fibrosis in Mice Via Suppression of TGF-beta 1/Smad Signaling and Activation of Nrf2/HO-1 Signaling

文献类型：期刊论文

作者Liu, Wenjing1,2; Wu, Jiajun2,3; Cao, Huiying2,3; Ma, Chen2,3; Wu, Zhitao1,2; Tian, Youxi4; Ma, Chenhui5; Qiu, Hong3,6,7; Pan, Guoyu1,2,3,8
刊名STEM CELLS AND DEVELOPMENT
出版日期2023-07-24
页码14
ISSN号1547-3287
关键词hepatic stellate cell activation liver fibrosis extracellular vesicles human-induced hepatocyte TGF-beta 1/Smad pathway Nrf2/HO-1 pathway
DOI10.1089/scd.2023.0110
通讯作者Qiu, Hong(hongqiu@simm.ac.cn) ; Pan, Guoyu(gypan@simm.ac.cn)
英文摘要Liver fibrosis is a wound-healing response caused by persistent liver injury and often occurs in chronic liver diseases. Effective treatments for liver fibrosis are still pending. Recent studies have revealed that extracellular vesicles (EVs) derived from primary hepatocytes (Hep-EVs) have therapeutic potential for multiple liver diseases. However, Hep-EVs are difficult to manufacture in bulk because of the limited sources of primary hepatocytes. Human-induced hepatocytes (hiHep) are hepatocyte-like cells that can expand in vitro, and their cell culture supernatant is thus an almost unlimited resource for EVs. This study aimed to investigate the potential therapeutic effects of EVs derived from hiHeps. hiHep-EVs inhibited the expression of inflammatory genes and the secretion of inflammation-related cytokines, and suppressed the activation of hepatic stellate cells by inhibiting the transforming growth factor (TGF)-beta 1/Smad signaling pathway. The anti-inflammatory and antifibrotic effects of hiHep-EVs were similar to those of mesenchymal stem cell-EVs. Furthermore, the administration of hiHep-EVs ameliorated oxidative stress, inflammation, and fibrosis in a CCl4-induced liver fibrosis mouse model. The expression of alpha smooth muscle actin, collagen I, and collagen III was reduced, which may be attributed to the regulation of matrix metalloproteinase ( MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 by hiHep-EVs, and the protein expression of Nrf2, HO-1, and NQO1 was increased. Taken together, our results suggested that hiHep-EVs alleviated liver fibrosis by activating the Nrf2/HO-1 signaling pathway and inhibiting the TGF-b1/Smad signaling pathway. This study revealed the hepatoprotective effect of hiHep-EVs, and provided a new approach to treating liver fibrosis.
WOS关键词HEPATIC STELLATE CELLS ; STEM-CELLS ; EXOSOMES ; MECHANISMS ; IMATINIB ; THERAPY ; LINES
资助项目National Science Foundation of China[82173878] ; Organ Reconstruction and Manufacturing'' Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16020205]
WOS研究方向Cell Biology ; Hematology ; Research & Experimental Medicine ; Transplantation
语种英语
出版者MARY ANN LIEBERT, INC
WOS记录号WOS:001035367700001
源URL[http://119.78.100.183/handle/2S10ELR8/306872]  
专题中国科学院上海药物研究所
通讯作者Qiu, Hong; Pan, Guoyu
作者单位1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
3.Univ Chinese Acad Sci, Beijing, Peoples R China
4.Guang Dong Med Univ, Sch Pharm, Dongguan, Peoples R China
5.Univ Nottingham Ningbo China, Dept Chem & Environm Engn, Ningbo, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Based Drug Res Ctr, Shanghai, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Based Drug Res Ctr, 555 Zuchongzhi Rd, Shanghai 200031, Peoples R China
8.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Wenjing,Wu, Jiajun,Cao, Huiying,et al. Human-Induced Hepatocytes-Derived Extracellular Vesicles Ameliorated Liver Fibrosis in Mice Via Suppression of TGF-beta 1/Smad Signaling and Activation of Nrf2/HO-1 Signaling[J]. STEM CELLS AND DEVELOPMENT,2023:14.
APA Liu, Wenjing.,Wu, Jiajun.,Cao, Huiying.,Ma, Chen.,Wu, Zhitao.,...&Pan, Guoyu.(2023).Human-Induced Hepatocytes-Derived Extracellular Vesicles Ameliorated Liver Fibrosis in Mice Via Suppression of TGF-beta 1/Smad Signaling and Activation of Nrf2/HO-1 Signaling.STEM CELLS AND DEVELOPMENT,14.
MLA Liu, Wenjing,et al."Human-Induced Hepatocytes-Derived Extracellular Vesicles Ameliorated Liver Fibrosis in Mice Via Suppression of TGF-beta 1/Smad Signaling and Activation of Nrf2/HO-1 Signaling".STEM CELLS AND DEVELOPMENT (2023):14.

入库方式： OAI收割

来源：上海药物研究所

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