{"title":"Adipose-derived mesenchymal stem cell-secreted extracellular vesicles alleviate non-alcoholic fatty liver disease <i>via</i> delivering miR-223-3p.","authors":"Qinghui Niu, Ting Wang, Zhiqiang Wang, Feng Wang, Deyu Huang, Huali Sun, Hanyun Liu","doi":"10.1080/21623945.2022.2098583","DOIUrl":null,"url":null,"abstract":"<p><p>Increasing studies have identified the potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in non-alcoholic fatty liver disease (NAFLD) treatment. Hence, we further focused on the potential of adipose-derived MSC (ADSC)-EVs in NAFLD by delivering miR-223-3p. The uptake of isolated ADSC-EVs by hepatocytes was assessed, and the expression of miR-223-3p in ADSC-EVs and hepatocytes was characterized. It was established that miR-223-3p, enriched in ADSC-EVs, could be delivered by ADSC-EVs into hepatocytes. Using co-culture system and gain-of-function approach, we evaluated the effect of ADSC-EVs carrying miR-223-3p on lipid accumulation and liver fibrosis in pyrrolizidine alkaloids (PA)-induced hepatocytes and a high-fat diet-induced NAFLD mouse model. Bioinformatics websites and dual-luciferase reporter gene assay were performed to determine the interactions between miR-223-3p and E2F1, which was further validated by rescue experiments. ADSC-EVs containing miR-223-3p displayed suppressive effects on lipid accumulation and liver fibrosis through E2F1 inhibition, since E2F1 was demonstrated as a target gene of miR-223-3p. The protective role of ADSC-EVs by delivering miR-223-3p was then confirmed in the mouse model. Collectively, this study elucidated that ADSC-EVs delayed the progression NAFLD through the delivery of anti-fibrotic miR-223-3p and subsequent E2F1 suppression, which may suggest miR-223-3p-loaded ADSC-EVs to be a potential therapeutic approach for NAFLD.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481107/pdf/","citationCount":"12","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Adipocyte","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/21623945.2022.2098583","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 12
Abstract
Increasing studies have identified the potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in non-alcoholic fatty liver disease (NAFLD) treatment. Hence, we further focused on the potential of adipose-derived MSC (ADSC)-EVs in NAFLD by delivering miR-223-3p. The uptake of isolated ADSC-EVs by hepatocytes was assessed, and the expression of miR-223-3p in ADSC-EVs and hepatocytes was characterized. It was established that miR-223-3p, enriched in ADSC-EVs, could be delivered by ADSC-EVs into hepatocytes. Using co-culture system and gain-of-function approach, we evaluated the effect of ADSC-EVs carrying miR-223-3p on lipid accumulation and liver fibrosis in pyrrolizidine alkaloids (PA)-induced hepatocytes and a high-fat diet-induced NAFLD mouse model. Bioinformatics websites and dual-luciferase reporter gene assay were performed to determine the interactions between miR-223-3p and E2F1, which was further validated by rescue experiments. ADSC-EVs containing miR-223-3p displayed suppressive effects on lipid accumulation and liver fibrosis through E2F1 inhibition, since E2F1 was demonstrated as a target gene of miR-223-3p. The protective role of ADSC-EVs by delivering miR-223-3p was then confirmed in the mouse model. Collectively, this study elucidated that ADSC-EVs delayed the progression NAFLD through the delivery of anti-fibrotic miR-223-3p and subsequent E2F1 suppression, which may suggest miR-223-3p-loaded ADSC-EVs to be a potential therapeutic approach for NAFLD.
期刊介绍:
Adipocyte recognizes that the adipose tissue is the largest endocrine organ in the body, and explores the link between dysfunctional adipose tissue and the growing number of chronic diseases including diabetes, hypertension, cardiovascular disease and cancer. Historically, the primary function of the adipose tissue was limited to energy storage and thermoregulation. However, a plethora of research over the past 3 decades has recognized the dynamic role of the adipose tissue and its contribution to a variety of physiological processes including reproduction, angiogenesis, apoptosis, inflammation, blood pressure, coagulation, fibrinolysis, immunity and general metabolic homeostasis. The field of Adipose Tissue research has grown tremendously, and Adipocyte is the first international peer-reviewed journal of its kind providing a multi-disciplinary forum for research focusing exclusively on all aspects of adipose tissue physiology and pathophysiology. Adipocyte accepts high-profile submissions in basic, translational and clinical research.