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免疫调节性细胞外囊泡在肝纤维化发病机制中的作用的新见解。

Novel insights into the role of immunomodulatory extracellular vesicles in the pathogenesis of liver fibrosis.

作者信息

Li Jiaxuan, Yuan Yue, Fu Qinggang, Chen Min, Liang Huifang, Chen Xiaoping, Long Xin, Zhang Bixiang, Zhao Jianping, Chen Qian

机构信息

Division of Gastroenterology, Department of Internal Medicine at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

出版信息

Biomark Res. 2024 Oct 12;12(1):119. doi: 10.1186/s40364-024-00669-8.

DOI:10.1186/s40364-024-00669-8
PMID:39396032
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11470730/
Abstract

Liver fibrosis, a chronic and long-term disease, can develop into hepatocellular carcinoma (HCC) and ultimately lead to liver failure. Early diagnosis and effective treatment still face significant challenges. Liver inflammation leads to liver fibrosis through continuous activation of hepatic stellate cells (HSCs) and the accumulation of immune cells. Intracellular communication among various immune cells is important for mediating the inflammatory response during fibrogenesis. Extracellular vesicles (EVs), which are lipid bilayer membrane-enclosed particles naturally secreted by cells, make great contributions to cell-cell communication and the transport of bioactive molecules. Nearly all the cells that participate in liver fibrosis release EVs loaded with lipids, proteins, and nucleic acids. EVs from hepatocytes, immune cells and stem cells are involved in mediating the inflammatory microenvironment of liver fibrosis. Recently, an increasing number of extracellular vesicle-based clinical applications have emerged, providing promising cell-free diagnostic and therapeutic tools for liver fibrosis because of their crucial role in immunomodulation during pathogenesis. The advantages of extracellular vesicle-based therapies include stability, biocompatibility, low cytotoxicity, and minimal immunogenicity, which highlight their great potential for drug delivery and specific treatments for liver fibrosis. In this review, we summarize the complex biological functions of EVs in the inflammatory response in the pathogenesis of liver fibrosis and evaluate the potential of EVs in the diagnosis and treatment of liver fibrosis.

摘要

肝纤维化是一种慢性长期疾病,可发展为肝细胞癌(HCC)并最终导致肝衰竭。早期诊断和有效治疗仍然面临重大挑战。肝脏炎症通过肝星状细胞(HSCs)的持续激活和免疫细胞的积累导致肝纤维化。各种免疫细胞之间的细胞内通讯对于介导纤维化过程中的炎症反应很重要。细胞外囊泡(EVs)是细胞自然分泌的脂质双层膜包裹的颗粒,对细胞间通讯和生物活性分子的运输有很大贡献。几乎所有参与肝纤维化的细胞都会释放载有脂质、蛋白质和核酸的EVs。来自肝细胞、免疫细胞和干细胞的EVs参与介导肝纤维化的炎症微环境。最近,越来越多基于细胞外囊泡的临床应用出现,由于它们在发病机制中的免疫调节中起关键作用,为肝纤维化提供了有前景的无细胞诊断和治疗工具。基于细胞外囊泡的疗法的优点包括稳定性、生物相容性、低细胞毒性和最小免疫原性,这突出了它们在肝纤维化药物递送和特异性治疗方面的巨大潜力。在这篇综述中,我们总结了EVs在肝纤维化发病机制中的炎症反应中的复杂生物学功能,并评估了EVs在肝纤维化诊断和治疗中的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce7/11470730/581239e866c4/40364_2024_669_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce7/11470730/9eb155652ebd/40364_2024_669_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce7/11470730/438ce4faab9f/40364_2024_669_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce7/11470730/581239e866c4/40364_2024_669_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce7/11470730/9eb155652ebd/40364_2024_669_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce7/11470730/438ce4faab9f/40364_2024_669_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ce7/11470730/581239e866c4/40364_2024_669_Fig3_HTML.jpg

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Biomolecules. 2024 Feb 26;14(3):277. doi: 10.3390/biom14030277.
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MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation.间充质干细胞衍生的外泌体通过抑制辅助性T细胞17分化减轻原发性硬化性胆管炎中的肝纤维化。
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源自肿瘤相关巨噬细胞的外泌体:在人类癌症中的生物发生、功能及治疗意义
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