Bone marrow mesenchymal stem cell-derived exosomes alleviate hyperoxia-induced lung injury via the manipulation of microRNA-425

作者：Wu, Yunfei; Li, Jun; Yuan, Rui; Deng, Zihui; Wu, Xu^*

来源：Archives of Biochemistry and Biophysics, 2021, 697: 108712.

DOI：10.1016/j.abb.2020.108712

• Hyperoxia-induced lung injury
• Bone marrow mesenchymal stem cell-derived exosomes
• microRNA-425
• PTEN
• PI3K/AKT signaling Pathway

Background: Hypemxia-induced lung injury (HILI) is an acute lung injury (LI) induced by extended periods of exposure to hypemxia. 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.

• 单位
  南方医科大学