Mesenchymal stem cell-derived small extracellular vesicles reduced hepatic lipid accumulation in MASLD by suppressing mitochondrial fission.

IF 7.1 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Research & Therapy Pub Date : 2025-03-05 DOI:10.1186/s13287-025-04228-2

Yifei Chen, Fuji Yang, Yanjin Wang, Yujie Shi, Likang Liu, Wei Luo, Jing Zhou, Yongmin Yan

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引用次数: 0

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease characterized by lipid accumulation in liver cells. Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) have great potential in repairing and regenerating liver diseases. However, it is still unclear whether MSC-sEV can inhibit hepatocyte lipid accumulation by regulating mitochondrial fission.

Methods: We investigated the effects of MSC-sEV on mitochondrial fission and its potential mechanism in lipotoxic hepatocytes and high-fat diet (HFD)-induced MASLD mice.

Results: We found that MSC-sEV can effectively inhibit the expression of the Dynamin-related protein 1 (DRP1), thereby reducing mitochondrial fission, mitochondrial damage, and lipid deposition in lipotoxic hepatocytes and livers of HFD-induced MASLD in mice. Further mechanistic studies revealed that RING finger protein 31 (RNF31) played a crucial role in mediating the inhibitory effect of MSC-sEV on DRP1 and mitochondrial fission. RNF31 can suppress DRP1 expression and mitochondrial fission, thereby improving mitochondrial dysfunction and reducing hepatocyte lipid deposition. These findings suggest that MSC-sEV may downregulate hepatocyte DRP1-mediated mitochondrial fission by transporting RNF31, ultimately inhibiting hepatocyte lipid accumulation.

Conclusions: The insights from this study provide a new perspective on the mechanism of MSC-sEV in reducing lipid accumulation and offer a potential therapeutic target by targeting DRP1 to inhibit hepatocyte steatosis and the progression of MASLD.

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间充质干细胞衍生的细胞外小泡通过抑制线粒体裂变减少MASLD的肝脂质积累。

背景：代谢功能障碍相关脂肪变性肝病（MASLD）是一种以肝细胞脂质积累为特征的慢性肝病。人脐带间充质干细胞衍生的小细胞外囊泡（MSC-sEV）在肝脏疾病的修复和再生中具有巨大的潜力。然而，MSC-sEV是否能通过调节线粒体裂变抑制肝细胞脂质积累尚不清楚。方法：研究MSC-sEV对脂毒性肝细胞和高脂饮食（HFD）诱导的MASLD小鼠线粒体分裂的影响及其可能机制。结果：我们发现MSC-sEV能有效抑制动力蛋白相关蛋白1 （Dynamin-related protein 1, DRP1）的表达，从而减少hfd诱导的小鼠脂毒性肝细胞和肝脏的线粒体分裂、线粒体损伤和脂质沉积。进一步的机制研究表明，RING finger protein 31 （RNF31）在介导MSC-sEV对DRP1和线粒体裂变的抑制作用中发挥了至关重要的作用。RNF31可以抑制DRP1的表达和线粒体分裂，从而改善线粒体功能障碍，减少肝细胞脂质沉积。这些发现表明MSC-sEV可能通过转运RNF31下调肝细胞drp1介导的线粒体分裂，最终抑制肝细胞脂质积累。结论：本研究的见解为MSC-sEV减少脂质积累的机制提供了新的视角，并提供了通过靶向DRP1抑制肝细胞脂肪变性和MASLD进展的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Research & Therapy CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

13.20

自引率

8.00%

发文量

525

审稿时长

1 months

期刊介绍： Stem Cell Research & Therapy serves as a leading platform for translational research in stem cell therapies. This international, peer-reviewed journal publishes high-quality open-access research articles, with a focus on basic, translational, and clinical research in stem cell therapeutics and regenerative therapies. Coverage includes animal models and clinical trials. Additionally, the journal offers reviews, viewpoints, commentaries, and reports.