4.7 Article

Extracellular vesicle-transmitted miR-671-5p alleviates lung inflammation and injury by regulating the AAK1/NF-KB axis

Journal

MOLECULAR THERAPY
Volume 31, Issue 5, Pages 1365-1382

Publisher

CELL PRESS
DOI: 10.1016/j.ymthe.2023.01.025

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Menstrual blood-derived stem cells can alleviate acute lung inflammation and injury through their extracellular vesicle-transmitted miR-671-5p. This miRNA directly targets AAK1 and regulates the activation of NF-kB signaling. This study provides insights into the molecular basis of how extracellular vesicles from mesenchymal stem cells improve pulmonary inflammatory injury and highlights the functional importance of the miR-671-5p/AAK1 axis.
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 bloodderived stem cells on lipopolysaccharide (LPS)-induced pulmonary inflammatory injury. Mechanistically, miR-6715p directly targets the kinase AAK1 for post-transcriptional degradation. AAK1 is found to positively regulate the activation of nuclear factor kB (NF-kB) signaling by controlling the stability of the inhibitory protein IkBa. 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.

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