Affiliations 

  • 1 Henan Joint International Research Laboratory of Stem Cell Medicine, School of Medical Engineering, Xinxiang Medical University, Xinxiang 453003, China; Lung Stem Cells and Gene Therapy Group, Department of Biomedical Sciences, Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, SAINS@Bertam, 13200 Kepala Batas, Penang, Malaysia; Stem Cells and Biotherapy Engineering Research Center of Henan, National Joint Engineering Laboratory of Stem Cells and Biotherapy, School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China
  • 2 Henan Joint International Research Laboratory of Stem Cell Medicine, School of Medical Engineering, Xinxiang Medical University, Xinxiang 453003, China. Electronic address: zhuxinxing0202@163.com
  • 3 Henan Joint International Research Laboratory of Stem Cell Medicine, School of Medical Engineering, Xinxiang Medical University, Xinxiang 453003, China
  • 4 Lung Stem Cells and Gene Therapy Group, Department of Biomedical Sciences, Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, SAINS@Bertam, 13200 Kepala Batas, Penang, Malaysia. Electronic address: badrul@usm.my
  • 5 Henan Joint International Research Laboratory of Stem Cell Medicine, School of Medical Engineering, Xinxiang Medical University, Xinxiang 453003, China; Stem Cells and Biotherapy Engineering Research Center of Henan, National Joint Engineering Laboratory of Stem Cells and Biotherapy, School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China. Electronic address: linjtlin@126.com
Mol Ther, 2023 May 03;31(5):1365-1382.
PMID: 36733250 DOI: 10.1016/j.ymthe.2023.01.025

Abstract

Mesenchymal stem cells regulate remote intercellular signaling communication via their secreted extracellular vesicles. Here, we report that menstrual blood-derived stem cells alleviate acute lung inflammation and injury via their extracellular vesicle-transmitted miR-671-5p. Disruption of this abundantly expressed miR-671-5p dramatically reduced the ameliorative effect of extracellular vesicles released by menstrual blood-derived stem cells on lipopolysaccharide (LPS)-induced pulmonary inflammatory injury. Mechanistically, miR-671-5p directly targets the kinase AAK1 for post-transcriptional degradation. AAK1 is found to positively regulate the activation of nuclear factor κB (NF-κB) signaling by controlling the stability of the inhibitory protein IκBα. This study identifies a potential molecular basis of how extracellular vesicles derived from mesenchymal stem cells improve pulmonary inflammatory injury and highlights the functional importance of the miR-671-5p/AAK1 axis in the progression of pulmonary inflammatory diseases. More importantly, this study provides a promising cell-based approach for the treatment of pulmonary inflammatory disorders through an extracellular vesicle-dependent pathway.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.