Bone marrow mesenchymal stem cell-derived exosomes improve renal fibrosis by reducing the polarisation of M1 and M2 macrophages through the activation of EP2 receptors

IF 3.8 4区工程技术 Q1 BIOCHEMICAL RESEARCH METHODS IET nanobiotechnology Pub Date : 2021-12-04 DOI:10.1049/nbt2.12071

Yuqing Lu, Lulu Yang, Xiao Chen, Jing Liu, Anqi Nie, Xiaolan Chen

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引用次数: 5

Abstract

Renal fibrosis is the pathological outcome of most end-stage renal diseases, yet there are still limited therapeutic options for it. In recent years, bone marrow mesenchymal stem cell-derived exosomes (BM-MSCs) have received much attention. Here, we investigate the therapeutic effect of BM-MSCs on unilateral ureteral occlusion (UUO)-induced interstitial fibrosis in the kidney by modulating prostaglandin E2 receptor 2 (EP2). Renal pathological changes were evident in the UUO group compared to the control group, with significantly increased expression of α-smooth muscle actin (α-SMA), fibronectin, Ep2 and F4/80⁺CD86⁺ and F4/80⁺CD206⁺ cells in the UUO group (p< 0.05). Pathological changes were alleviated and F4/80⁺CD86⁺ and F480/⁺CD206⁺ cells were reduced after exosome or EP2 agonist intervention compared to the UUO group. These data were further confirmed in vitro. Compared to the lipopolysaccharide (LPS) group and the LPS + exosome + Ah6809 group, the lipopolysaccharide (LPS) + exosome group and the LPS + butaprost group showed a significant decrease in α-SMA expression, a decrease in the number of F4/80⁺CD86⁺ and F4/80⁺CD206⁺ cells, a decrease in interleukin (IL)-6 and an increase in IL-10 levels. Therefore, we conclude that BM-MSCs can reduce the polarization of M1 and M2 macrophages by activating EP2 receptors, thereby ameliorating renal fibrosis.

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骨髓间充质干细胞衍生的外泌体通过激活EP2受体，减少M1和M2巨噬细胞的极化，从而改善肾纤维化

肾纤维化是大多数终末期肾脏疾病的病理结果，但仍然有有限的治疗选择。近年来，骨髓间充质干细胞衍生外泌体(BM-MSCs)受到广泛关注。在这里，我们通过调节前列腺素E2受体2 (EP2)来研究BM-MSCs对单侧输尿管阻塞(UUO)诱导的肾间质纤维化的治疗作用。与对照组相比，UUO组肾脏病理改变明显，α-平滑肌肌动蛋白(α-SMA)、纤维连接蛋白、Ep2及F4/80+CD86+、F4/80+CD206+细胞表达显著升高(p < 0.05);0.05)。与UUO组相比，外泌体或EP2激动剂干预后，病理改变减轻，F4/80+CD86+和F480/+CD206+细胞减少。这些数据在体外得到进一步证实。与脂多糖(LPS)组和脂多糖+外泌体+ Ah6809组相比，脂多糖+外泌体组和脂多糖+ butaprost组α-SMA表达显著降低，F4/80+CD86+和F4/80+CD206+细胞数量减少，白细胞介素(IL)-6降低，IL-10水平升高。因此，我们认为BM-MSCs可以通过激活EP2受体减少M1和M2巨噬细胞的极化，从而改善肾纤维化。

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来源期刊

IET nanobiotechnology 工程技术-纳米科技

CiteScore

6.20

自引率

4.30%

发文量

审稿时长

1 months

期刊介绍： Electrical and electronic engineers have a long and illustrious history of contributing new theories and technologies to the biomedical sciences. This includes the cable theory for understanding the transmission of electrical signals in nerve axons and muscle fibres; dielectric techniques that advanced the understanding of cell membrane structures and membrane ion channels; electron and atomic force microscopy for investigating cells at the molecular level. Other engineering disciplines, along with contributions from the biological, chemical, materials and physical sciences, continue to provide groundbreaking contributions to this subject at the molecular and submolecular level. Our subject now extends from single molecule measurements using scanning probe techniques, through to interactions between cells and microstructures, micro- and nano-fluidics, and aspects of lab-on-chip technologies. The primary aim of IET Nanobiotechnology is to provide a vital resource for academic and industrial researchers operating in this exciting cross-disciplinary activity. We can only achieve this by publishing cutting edge research papers and expert review articles from the international engineering and scientific community. To attract such contributions we will exercise a commitment to our authors by ensuring that their manuscripts receive rapid constructive peer opinions and feedback across interdisciplinary boundaries. IET Nanobiotechnology covers all aspects of research and emerging technologies including, but not limited to: Fundamental theories and concepts applied to biomedical-related devices and methods at the micro- and nano-scale (including methods that employ electrokinetic, electrohydrodynamic, and optical trapping techniques) Micromachining and microfabrication tools and techniques applied to the top-down approach to nanobiotechnology Nanomachining and nanofabrication tools and techniques directed towards biomedical and biotechnological applications (e.g. applications of atomic force microscopy, scanning probe microscopy and related tools) Colloid chemistry applied to nanobiotechnology (e.g. cosmetics, suntan lotions, bio-active nanoparticles) Biosynthesis (also known as green synthesis) of nanoparticles; to be considered for publication, research papers in this area must be directed principally towards biomedical research and especially if they encompass in vivo models or proofs of concept. We welcome papers that are application-orientated or offer new concepts of substantial biomedical importance Techniques for probing cell physiology, cell adhesion sites and cell-cell communication Molecular self-assembly, including concepts of supramolecular chemistry, molecular recognition, and DNA nanotechnology Societal issues such as health and the environment Special issues. Call for papers: Smart Nanobiosensors for Next-generation Biomedical Applications - https://digital-library.theiet.org/files/IET_NBT_CFP_SNNBA.pdf Selected extended papers from the International conference of the 19th Asian BioCeramic Symposium - https://digital-library.theiet.org/files/IET_NBT_CFP_ABS.pdf