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

  • Arch Biochem Biophys. 2021 Jan 15;697:108712. doi: 10.1016/j.abb.2020.108712.
Yunfei Wu  1 ,  Jun Li  2 ,  Rui Yuan  3 ,  Zihui Deng  4 ,  Xu Wu  5
Affiliations
  • 1. Department of Thoracic Surgery/Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of Thoracic Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
  • 2. Department of Thoracic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, 510630, China.
  • 3. Department of Critical Care Medicine, General Hospital of the Chinese People's Liberation Army, Beijing, 100853, China.
  • 4. Biochemistry Department of Graduate School, General Hospital of the Chinese People's Liberation Army, Beijing, 100853, China.
  • 5. Department of Thoracic Surgery/Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China. Electronic address: [email protected].
PMID: 33264631 DOI: 10.1016/j.abb.2020.108712
Abstract

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.

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