Phosphatidylserine-mediated uptake of extracellular vesicles by hepatocytes ameliorates liver ischemia-reperfusion injury.

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Apoptosis Pub Date : 2024-10-13 DOI:10.1007/s10495-024-02030-8

Rongrong Li, Chen Wang, Xiaoniao Chen, Enze Fu, Kaiyue Zhang, Hongyan Tao, Zhibo Han, Zhong-Chao Han, Zongjin Li

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Abstract

Compelling evidence suggests that mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) promote regeneration in animal models of liver injury by delivering signaling molecules. However, their target cells and uptake mechanism remain elusive. In this study, MSC-EVs were intravenously administered in a mouse model of liver ischemia-reperfusion injury (IRI). Our results revealed that MSC-EVs exhibit enhanced liver targeting in IRI mice, and injured hepatocytes display a greater capacity for MSC-EV uptake. We found that phosphatidylserine (PS) displayed on the exterior of injured hepatocytes promotes MSC-EV internalization, possibly by binding to MFGE8, a protein expressed on the MSC-EV membrane. Furthermore, the therapeutic effect of MSC-EVs on liver IRI is highly dependent on this PS-mediated uptake pathway. Our findings provide evidence that MSC-EVs preferentially target injured hepatocytes, relying on a PS-dependent uptake route to exert hepatoprotective effects, which are critical for the future design of EV-based therapeutic strategies for liver IRI.

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磷脂酰丝氨酸介导的肝细胞吸收细胞外囊泡可改善肝脏缺血再灌注损伤。

令人信服的证据表明，间充质干细胞衍生的细胞外囊泡（MSC-EVs）通过传递信号分子促进肝损伤动物模型的再生。然而，它们的靶细胞和吸收机制仍然难以捉摸。本研究在肝脏缺血再灌注损伤（IRI）小鼠模型中静脉注射间充质干细胞-EV。我们的研究结果表明，间充质干细胞-EV在IRI小鼠肝脏靶向性增强，损伤肝细胞对间充质干细胞-EV的摄取能力更强。我们发现，损伤肝细胞外部的磷脂酰丝氨酸（PS）可促进间充质干细胞-EV的内化，这可能是通过与间充质干细胞-EV膜上表达的蛋白MFGE8结合实现的。此外，间充质干细胞-EV对肝脏IRI的治疗效果高度依赖于这种PS介导的吸收途径。我们的研究结果提供了证据，表明间充质干细胞-EV优先靶向损伤的肝细胞，依靠PS依赖性摄取途径发挥保肝作用，这对未来设计基于EV的肝脏IRI治疗策略至关重要。

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

Apoptosis 生物-生化与分子生物学

CiteScore

9.10

自引率

4.20%

发文量

审稿时长

1 months

期刊介绍： Apoptosis, a monthly international peer-reviewed journal, focuses on the rapid publication of innovative investigations into programmed cell death. The journal aims to stimulate research on the mechanisms and role of apoptosis in various human diseases, such as cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis, and aging. The Editor-In-Chief acknowledges the importance of advancing clinical therapies for apoptosis-related diseases. Apoptosis considers Original Articles, Reviews, Short Communications, Letters to the Editor, and Book Reviews for publication.