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

• Published in: Molecular therapy Vol. 31; no. 5; pp. 1365 - 1382
• Main Authors: Lian, Jie, Zhu, Xinxing, Du, Jiang, Huang, Beijia, Zhao, Fengting, Ma, Chunya, Guo, Rui, Zhang, Yangxia, Ji, Longkai, Yahaya, Badrul Hisham, Lin, Juntang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.05.2023; American Society of Gene & Cell Therapy
• Subjects: AAK1; extracellular vesicles; Extracellular Vesicles - genetics; Extracellular Vesicles - metabolism; Humans; Inflammation - genetics; Inflammation - metabolism; Inflammation - therapy; Lipopolysaccharides - pharmacology; Lung Injury; menstrual blood-derived stem cells; MicroRNAs - genetics; MicroRNAs - metabolism; miR-671-5p; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB signaling; Original; Pneumonia - genetics; Pneumonia - therapy; Protein Serine-Threonine Kinases; pulmonary inflammatory injury; pulmonary inflammatory injury; NF-κB signaling; AAK1; menstrual blood-derived stem cells; extracellular vesicles; miR-671-5p
• ISSN: 1525-0016; 1525-0024; 1525-0024
• DOI: 10.1016/j.ymthe.2023.01.025

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. [Display omitted] Menstrual blood-derived stem cells alleviate acute lung injury through extracellular vesicle-transmitted miR-671-5p, which directly targets AAK1 for degradation, and thus suppresses AAK1-mediated NF-κB signaling activation. These findings provide a promising cell-based approach for the treatment of pulmonary inflammatory injury.