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Lung-derived exosomes regulate the function of mesenchymal stem cells and alleviate phosgene-induced lung injury via miR-34c-3p
Journal of Biochemical and Molecular Toxicology ( IF 3.6 ) Pub Date : 2021-07-31 , DOI: 10.1002/jbt.22851
Zhi-Feng Jiang 1, 2, 3 , Yiru Shao 1, 2, 3 , Lin Zhang 1, 2, 3 , Jie Shen 1, 2, 3
Affiliation  

Phosgene may induce acute lung injury (ALI) when a person is exposed to it. Mesenchymal stem cells (MSCs) were affirmed to have therapeutic effects on phosgene-induced ALI. In a previous study, ALI exosomes have been confirmed to promote the proliferation and migration of MSCs. However, the mechanism of this phenomenon is still unclear. MicroRNAs (miRNAs) are essential in the physiological process of cells. In this study, lung-derived exosomes were isolated from phosgene-exposed and normal rats, respectively, through ultracentrifugation and cultured MSCs with these exosomes. We found that rno-miR-34c-3p was downregulated in MSCs cocultured with ALI exosomes. MiR-34c-3p inhibitor promoted the proliferation and migration of MSCs. Moreover, the dual-luciferase reporter assay demonstrated that miR-34c-3p regulated Janus kinase 1 (JAK1) expression. The miR-34c-3p inhibitor also significantly activated the JAK1/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In conclusion, ALI exosomes decrease the miR-34c-3p expression levels, influencing MSCs via the JAK1/STAT3 signaling pathway.

中文翻译:

肺源性外泌体通过 miR-34c-3p 调节间充质干细胞的功能并减轻光气诱导的肺损伤

当人接触光气时,可能会诱发急性肺损伤 (ALI)。间充质干细胞 (MSCs) 被证实对光气诱导的 ALI 具有治疗作用。在之前的一项研究中,ALI 外泌体已被证实可促进 MSCs 的增殖和迁移。然而,这一现象的机制尚不清楚。MicroRNAs (miRNAs) 在细胞的生理过程中是必不可少的。在这项研究中,分别通过超速离心从暴露于光气的大鼠和正常大鼠中分离出肺源性外泌体,并用这些外泌体培养 MSC。我们发现 rno-miR-34c-3p 在与 ALI 外泌体共培养的 MSC 中下调。MiR-34c-3p抑制剂促进MSCs的增殖和迁移。此外,双荧光素酶报告基因测定表明 miR-34c-3p 调节 Janus 激酶 1 (JAK1) 表达。miR-34c-3p 抑制剂还显着激活 JAK1/信号转导和转录激活因子 3 (STAT3) 信号通路。总之,ALI 外泌体降低 miR-34c-3p 表达水平,通过 JAK1/STAT3 信号通路影响 MSC。
更新日期:2021-09-15
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