Human Adipose Mesenchymal Stem Cells-derived Exosomes Ameliorate Hepatic Fibrosis by Regulating Choline Metabolism and PI3K/Akt/mTOR Pathway:Based on Transcriptomics and Metabolomics
作者单位：Department of Hepatobiliary-Pancreatic SurgeryCell Transplantation CenterSichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of China
会议名称：《2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会》
会议日期：2023年
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
摘 要：Liver fibrosis is a chronic liver disease with presence of the progressive wound healing response caused by liver ***,there are no approved therapies for liver *** derived from human adipose mesenchymal stem cells(hADMSCs-Exo) have displayed a prominent therapeutic effect on liver ***,few studies have evaluated therapeutic effect of hADMSCs-Exo in liver fibrosis and cirrhosis,and its precise mechanisms of action remains ***,we investigated in vitro and in vivo antifibrotic efficacy of hADMSCs-Exo,and identified important metabolic changes and the detailed mechanism through transcriptomic and metabolomic *** found hADMSCs-Exo could inhibit the proliferation of activated hepatic stellate cells,promote their apoptosis,arrest G1 phase,effectively inhibit the expression of profibrogenic proteins and epithelial-to-mesenchymal transition(EMT) in ***,it could significantly decrease the expression of collagen deposition and EMT progression,improve liver function and reduce liver inflammation in liver cirrhosis mice *** addition,Transcriptome analysis revealed that the key mechanism of hADMSCs-Exo anti-hepatic fibrosis was the regulation of PI3K/AKT/mTOR signaling *** analysis showed that hADMSCs-Exo affected the changes of metabolites in lipid metabolism and mainly regulated choline metabolism,which involved in PI3K/AKT/mTOR pathway to anti-liver ***,our study indicates that hADMSCs-Exo can attenuated hepatic stellate cell activation and suppressed 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.