间充质干细胞来源的外泌体递送 microRNA-130b-3p 对急性肺损伤起保护作用。
microRNA-130b-3p delivery by mesenchymal stem cells-derived exosomes confers protection on acute lung injury.
机构信息
Key Laboratory for Basic Science and Prevention of Perioperative Organ Disfunction Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China.
The Laboratory of Perioperative Medicine Research Center, Guangxi Medical University Affiliated Tumor Hospital & Oncology Medical College, Nanning, Guangxi, China.
出版信息
Autoimmunity. 2022 Dec;55(8):597-607. doi: 10.1080/08916934.2022.2094370. Epub 2022 Aug 26.
OBJECTIVE
Researchers have investigated miR-130b-3p in lung disease pathology, such as lung fibrosis. The present study was performed to elucidate the miR-130b-3p-involved mechanism in acute lung injury (ALI) through delivery by mesenchymal stem cells-derived exosomes (MSCs-Exo).
METHODS
ALI mouse models were induced via intratracheal administration of lipopolysaccharide (LPS) and treated with MSCs-Exo. Lung dry-wet (/) ratio, inflammatory factors in the bronchoalveolar lavage fluid, pathological damage and apoptosis in the lung tissues were analyzed. Expression levels of miR-130b-3p and TGFBR1 were measured in the mouse lung tissues, and the interaction between miR-130b-3p and TGFBR1 was studied.
RESULTS
MSCs-Exo relieved LPS-induced ALI in mice by reducing lung / ratio and inflammatory response, and attenuating lung tissue pathological damage and reducing the alveolar cell apoptosis. miR-130b-3p delivery by MSCs-Exo reduced LPS-induced ALI in mice. TGFBR1 was determined to be a downstream target gene of miR-130b-3p. Inhibition of TGFBR1 could remit LPS-induced ALI in mice. The protection mediated by MSCs-Exo carrying miR-130b-3p could be rescued by elevating TGFBR1 expression.
CONCLUSION
miR-130b-3p delivery by MSCs-Exo confers protection on ALI in mice via the downregulation of TGFBR1.
目的
研究人员已经研究了 miR-130b-3p 在肺部疾病病理学中的作用，如肺纤维化。本研究旨在通过间充质干细胞衍生的外泌体（MSCs-Exo）的递送来阐明 miR-130b-3p 在急性肺损伤（ALI）中的作用机制。
方法
通过气管内给予脂多糖（LPS）诱导 ALI 小鼠模型，并给予 MSCs-Exo 治疗。分析肺干湿（/）比、支气管肺泡灌洗液中的炎症因子、肺组织的病理损伤和细胞凋亡。测量小鼠肺组织中 miR-130b-3p 和 TGFBR1 的表达水平，并研究 miR-130b-3p 与 TGFBR1 之间的相互作用。
结果
MSCs-Exo 通过降低肺 / 比和炎症反应、减轻肺组织病理损伤和减少肺泡细胞凋亡，减轻 LPS 诱导的 ALI 小鼠的肺损伤。MSCs-Exo 递送的 miR-130b-3p 减少了 LPS 诱导的 ALI 小鼠的肺损伤。TGFBR1 被确定为 miR-130b-3p 的下游靶基因。抑制 TGFBR1 可缓解 LPS 诱导的 ALI 小鼠的肺损伤。MSCs-Exo 携带 miR-130b-3p 介导的保护作用可通过提高 TGFBR1 的表达得到挽救。
结论
MSCs-Exo 递送的 miR-130b-3p 通过下调 TGFBR1 对 LPS 诱导的 ALI 小鼠发挥保护作用。
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