Adipose-derived mesenchymal stem cell-secreted extracellular vesicles alleviate non-alcoholic fatty liver disease via delivering miR-223-3p.

IF 3.5 4区 生物学 Q2 ENDOCRINOLOGY & METABOLISM Adipocyte Pub Date : 2022-12-01 DOI:10.1080/21623945.2022.2098583
Qinghui Niu, Ting Wang, Zhiqiang Wang, Feng Wang, Deyu Huang, Huali Sun, Hanyun Liu
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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.

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脂肪源性间充质干细胞分泌的细胞外囊泡通过传递miR-223-3p缓解非酒精性脂肪肝疾病。
越来越多的研究已经确定了间充质干细胞衍生的细胞外囊泡(msc - ev)在非酒精性脂肪性肝病(NAFLD)治疗中的潜力。因此,我们进一步关注脂肪来源的MSC (ADSC)- ev通过递送miR-223-3p在NAFLD中的潜力。评估肝细胞对分离的adsc - ev的摄取情况,并表征miR-223-3p在adsc - ev和肝细胞中的表达。我们证实,在adsc - ev中富集的miR-223-3p可以通过adsc - ev传递到肝细胞中。通过共培养系统和功能获得法,我们评估了携带miR-223-3p的adsc - ev对吡罗里西定生物碱(PA)诱导的肝细胞和高脂肪饮食诱导的NAFLD小鼠模型中脂质积累和肝纤维化的影响。通过生物信息学网站和双荧光素酶报告基因检测来确定miR-223-3p与E2F1之间的相互作用,并通过救援实验进一步验证。含有miR-223-3p的adsc - ev通过抑制E2F1表现出对脂质积累和肝纤维化的抑制作用,因为E2F1被证明是miR-223-3p的靶基因。然后在小鼠模型中证实了adsc - ev通过传递miR-223-3p的保护作用。总的来说,这项研究阐明了adsc - ev通过传递抗纤维化miR-223-3p和随后的E2F1抑制来延缓NAFLD的进展,这可能表明负载miR-223-3p的adsc - ev是一种潜在的NAFLD治疗方法。
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来源期刊
Adipocyte
Adipocyte Medicine-Histology
CiteScore
6.50
自引率
3.00%
发文量
46
审稿时长
32 weeks
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.
期刊最新文献
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