Background

Hyperoxia-induced lung injury (HILI) is an acute lung injury (LI) induced by extended periods of exposure to hyperoxia. Alleviating LI by bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exos) and microRNAs (miRs) has been previously reported. This study is devised to probe the interaction between BMSCs-Exos and miR-425 in HILI.

Methods

Firstly, BMSCs-Exos were isolated and identified. Then, HILI rat models and RLE-6TN cell models were successfully established and treated by BMSCs-Exos. Afterwards, functional assays were conducted to explore cell biological behaviors in models, with miR-425 expression detected. Then, the target relation between miR-425 and PTEN was clarified by luciferase reporter assay. Eventually, expression of PTEN and the PI3K/Akt axis was assessed by Western blotting and qRT-PCR.

Results

BMSCs-Exos promoted miR-425 expression and attenuated HILI and H₂O₂ induced RLE-6TN cell injury as evidence by alleviated lung cell injury, decreased TUNEL-positive cells, induced cell viability and declined apoptosis (all p < 0.05). Besides, when miR-425 was knocked-down, the protective role of BMSCs-Exos in HILI was also reduced (all p < 0.05). miR-425 targeted PTEN mRNA, whose upregulation reversed the protective role of BMSCs-Exos in HILI (all p < 0.05). BMSCs-Exos improved the quenched levels of the PI3K/AKT axis in HILI (all p < 0.05).

Conclusion

Our data supported that miR-425 in BMSCs-Exos inhibits HILI by targeting PTEN and upregulating the PI3K/AKT axis. This study may provide personalized interventions for HILI remedy.

中文翻译：

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骨髓间充质干细胞来源的外来体通过操作microRNA-425减轻高氧诱导的肺损伤

背景

高氧血症引起的肺损伤（HILI）是长时间暴露于高氧血症引起的急性肺损伤（LI）。先前已报道过通过骨髓间充质干细胞来源的外来体（BMSCs-Exos）和microRNA（miRs）减轻LI。本研究旨在探讨HILI中BMSCs-Exos与miR-425之间的相互作用。

方法

首先，分离并鉴定了BMSCs-Exos。然后，成功建立了HILI大鼠模型和RLE-6TN细胞模型，并用BMSCs-Exos治疗。之后，进行功能测定以探索模型中的细胞生物学行为，并检测到miR-425表达。然后，通过荧光素酶报告基因分析阐明了miR-425和PTEN之间的靶标关系。最终，通过蛋白质印迹和qRT-PCR评估PTEN和PI3K / Akt轴的表达。

结果

BMSCs-Exos促进了miR-425的表达，并减轻了HILI和H ₂ O ₂诱导的RLE-6TN细胞损伤，减轻肺细胞损伤，减少TUNEL阳性细胞，诱导细胞活力并降低细胞凋亡的证据（所有p  <0.05）。此外，当敲低miR-425时，BMSCs-Exos在HILI中的保护作用也降低了（所有p  <0.05）。miR-425靶向PTEN mRNA，其上调逆转了BMSCs-Exos在HILI中的保护作用（所有p  <0.05）。BMSCs-Exos改善了HILI中PI3K / AKT轴的淬灭水平（所有p  <0.05）。

结论

我们的数据支持BMSCs-Exos中的miR-425通过靶向PTEN并上调PI3K / AKT轴来抑制HILI。这项研究可能为HILI补救提供个性化干预措施。