经脂多糖预处理的牙周韧带干细胞产生的胞外囊泡通过 PI3K/AKT 信号通路改善实验性结肠炎的炎症反应

IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY
International Journal of Nanomedicine Pub Date : 2024-11-18 eCollection Date: 2024-01-01 DOI:10.2147/IJN.S494321
Shuai Tang, Wenyu Feng, Zekun Li, Xinjuan Liu, Tong Yang, Fulan Wei, Gang Ding
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引用次数: 0

摘要

导言炎症性肠病是一种复杂的慢性炎症,其特点是肠道微生物群失调和免疫系统失调。近年来,从间充质干细胞中提取的细胞外囊泡(EVs)因其在免疫调节和组织修复方面的有益潜力而备受关注。本研究旨在评估经脂多糖(LPS)处理的牙周韧带干细胞(PDLSCs)衍生的EVs对结肠炎小鼠的治疗效果及其内在机制:使用 3.0% 右旋糖酐硫酸钠(DSS)建立小鼠结肠炎模型。方法:使用 3.0% 硫酸右旋糖酐钠(DSS)建立了小鼠结肠炎模型,诱导小鼠患上结肠炎后,通过尾静脉注射传统的 PDLSC 衍生 EVs(P-EVs)或 LPS 预处理的 PDLSC 衍生 EVs(LPS pre-EVs)对小鼠进行治疗。使用透射电子显微镜、纳米颗粒跟踪分析和 Western 印迹分析对这些 EVs 进行了表征。通过小动物活体成像、疾病活动指数(DAI)评分、组织病理学染色、qRT-PCR、16S rRNA 基因测序和质谱分析,对治疗效果和机制进行了评估:结果:LPS前EVs在形态、粒度分布和标志蛋白表达方面表现出典型的EVs特征。与P-EVs相比,LPS前EVs能显著改善DSS诱导的小鼠结肠炎的体重减轻、DAI评分、结肠长度和肛周症状。此外,LPS前EVs还能上调典型的M2巨噬细胞标志物精氨酸酶-1以及ZO-1、Occludin和Claudin-1等紧密连接蛋白的表达,增强肠道微生物的多样性,并能显著调节肠道蛋白的表达和PI3K/AKT信号通路的激活:结论:LPS前EVs在小鼠结肠炎模型中表现出明显的抗炎和组织修复作用。其潜在机制可能涉及巨噬细胞极化的调节、肠道屏障功能的维护、肠道微生物群的调节以及 PI3K/AKT 信号通路的激活。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Extracellular Vesicles Derived from Lipopolysaccharide-Pretreated Periodontal Ligament Stem Cells Ameliorate Inflammatory Responses in Experimental Colitis via the PI3K/AKT Signaling Pathway.

Introduction: Inflammatory bowel disease is a complex chronic inflammatory condition characterized by dysbiosis of the gut microbiota and dysregulation of immune system. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells have garnered significant attention for their beneficial potentials in immune modulation and tissue repair. This study aims to evaluate the therapeutic effects and underlying mechanisms of EVs derived from lipopolysaccharide (LPS)-pretreated periodontal ligament stem cells (PDLSCs) in mice with colitis.

Methods: A mouse model of colitis was established using 3.0% dextran sulfate sodium (DSS). Following the induction of colitis, mice were treated via tail vein injection with either conventional PDLSC-derived EVs (P-EVs) or LPS-pretreated PDLSC-derived EVs (LPS pre-EVs). The EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. The therapeutic effects and mechanisms were evaluated through a combination of small animal live imaging, disease activity index (DAI) scoring, histopathological staining, qRT-PCR, 16S rRNA gene sequencing, and mass spectrometry analysis.

Results: The LPS pre-EVs exhibited typical EVs characteristics in terms of morphology, particle size distribution, and marker protein expression. Compared to P-EVs, LPS pre-EVs significantly ameliorated weight loss, DAI scores, colon length, and perianal symptoms in DSS-induced murine colitis. Additionally, LPS pre-EVs up-regulated the expression of Arginase-1, a typical M2 macrophage marker, and tight junction proteins, including ZO-1, Occludin, and Claudin-1, enhanced gut microbial diversity, and significantly regulated intestinal protein expression and activation of the PI3K/AKT signaling pathway.

Conclusion: LPS pre-EVs exhibit significant anti-inflammatory and tissue repair effects in a mouse model of colitis. The underlying mechanisms may involve the regulation of macrophage polarization, maintenance of intestinal barrier function, modulation of the gut microbiota, and activation of the PI3K/AKT signaling pathway.

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来源期刊
International Journal of Nanomedicine
International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY
CiteScore
14.40
自引率
3.80%
发文量
511
审稿时长
1.4 months
期刊介绍: The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.
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