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Exosomes derived from human adipose mesenchymal stem cells ameliorate hepatic fibrosis by inhibiting PI3K/Akt/mTOR pathway and remodeling choline metabolism

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收录情况： ◇ SCIE

作者：
Zhang Zilong[1,2] * ; Shang Jin[1,2] * ; Yang Qinyan[1,2] * ; Dai Zonglin[1,2] ; Liang Yuxin[1,2] ; Lai Chunyou[1,2] ; Feng Tianhang[1,2] ; Zhong Deyuan[1,2] ; Zou Haibo[1,2] ; Sun Lelin[2] ; Su Yuhao[1,2] ; Yan Su[1,2] ; Chen Jie[3] ; Yao Yutong[1,2] ; Shi Ying[1,2] ; Huang Xiaolun[1,2] ;
机构： [1]Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital Affiliate to University of Electronic Science and Technology of China, Chengdu, 610042, Sichuan, China. [2]School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, Sichuan, China. [3]Department of Core laboratory, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, Sichuan, China
出处：
DOI： 10.1186/s12951-023-01788-4
ISSN：

关键词： Liver fibrosis Human adipose mesenchymal stem cells Exosomes Metabolomics Choline

摘要：
Liver fibrosis is a chronic liver disease with the presence of progressive wound healing response caused by liver injury. Currently, there are no approved therapies for liver fibrosis. Exosomes derived from human adipose mesenchymal stem cells (hADMSCs-Exo) have displayed a prominent therapeutic effect on liver diseases. However, few studies have evaluated therapeutic effect of hADMSCs-Exo in liver fibrosis and cirrhosis, and its precise mechanisms of action remain unclear. Herein, we investigated anti-fibrotic efficacy of hADMSCs-Exo in vitro and in vivo, and identified important metabolic changes and the detailed mechanism through transcriptomic and metabolomic profiling. We found hADMSCs-Exo could inhibit the proliferation of activated hepatic stellate cells through aggravating apoptosis and arresting G1 phase, effectively inhibiting the expression of profibrogenic proteins and epithelial-to-mesenchymal transition (EMT) in vitro. Moreover, it could significantly block collagen deposition and EMT process, improve liver function and reduce liver inflammation in liver cirrhosis mice model. The omics analysis revealed that the key mechanism of hADMSCs-Exo anti-hepatic fibrosis was the inhibition of PI3K/AKT/mTOR signaling pathway and affecting the changes of metabolites in lipid metabolism, and mainly regulating choline metabolism. CHPT1 activated by hADMSCs-Exo facilitated formation and maintenance of vesicular membranes. Thus, our study indicates that hADMSCs-Exo can attenuate hepatic stellate cell activation and suppress the progression of liver fibrosis, which holds the significant potential of hADMSCs-Exo for use as extracellular nanovesicles-based therapeutics in the treatment of liver fibrosis and possibly other intractable chronic liver diseases.© 2023. The Author(s).

基金：
Sichuan Province Science and Technology Support Program (No. 2018HH0062) to XH; Sichuan Science and Technology Program (No. 2021YFH0187) to YS; Medico-Engineering Cooperation Funds from University of Electronic Science and Technology of China (No. ZYGX- 2021YGCX018) to YS; and the Fundamental Research Funds for the Central Universities (No. ZYGX2020KYQD002) to YS.
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外文
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中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 生物学
小类 | 1 区 生物工程与应用微生物 2 区 纳米科技
最新[2023]版：
大类 | 1 区 生物学
小类 | 1 区 生物工程与应用微生物 2 区 纳米科技
JCR分区：
出版当年[2023]版：
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 NANOSCIENCE & NANOTECHNOLOGY
最新[2023]版：
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 NANOSCIENCE & NANOTECHNOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2022版]

第一作者：
第一作者机构： [1]Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital Affiliate to University of Electronic Science and Technology of China, Chengdu, 610042, Sichuan, China. [2]School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, Sichuan, China.
共同第一作者：
通讯作者：
通讯机构： [1]Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital Affiliate to University of Electronic Science and Technology of China, Chengdu, 610042, Sichuan, China. [2]School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, Sichuan, China.
推荐引用方式(GB/T 7714)：
Zhang Zilong,Shang Jin,Yang Qinyan,et al.Exosomes derived from human adipose mesenchymal stem cells ameliorate hepatic fibrosis by inhibiting PI3K/Akt/mTOR pathway and remodeling choline metabolism[J].JOURNAL OF NANOBIOTECHNOLOGY.2023,21(1):doi:10.1186/s12951-023-01788-4.
APA：
Zhang Zilong,Shang Jin,Yang Qinyan,Dai Zonglin,Liang Yuxin...&Huang Xiaolun.(2023).Exosomes derived from human adipose mesenchymal stem cells ameliorate hepatic fibrosis by inhibiting PI3K/Akt/mTOR pathway and remodeling choline metabolism.JOURNAL OF NANOBIOTECHNOLOGY,21,(1)
MLA：
Zhang Zilong,et al."Exosomes derived from human adipose mesenchymal stem cells ameliorate hepatic fibrosis by inhibiting PI3K/Akt/mTOR pathway and remodeling choline metabolism".JOURNAL OF NANOBIOTECHNOLOGY 21..1(2023)

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