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  • Title: MiR-223-3p-loaded exosomes from bronchoalveolar lavage fluid promote alveolar macrophage autophagy and reduce acute lung injury by inhibiting the expression of STK39.
    Author: He N, Tan H, Deng X, Shu L, Qing B, Liang H.
    Journal: Hum Cell; 2022 Nov; 35(6):1736-1751. PubMed ID: 35932362.
    Abstract:
    This study investigated the molecular mechanism by which bronchoalveolar lavage fluid exosomes (BALF-exo) alleviated acute lung injury (ALI). BALF-exo was isolated from mice. LPS was used to induce inflammation in rat alveolar macrophages (NR8383). NR8383 cell models were treated with BALF-exo or BALF-exo loaded with miR-223-3p mimics/inhibitors, or STK39 was overexpressed in NR8383 cells before LPS and BALF-exo treatment. These cells were subjected to apoptosis, autophagy, and inflammation assays. RNA immunoprecipitation and dual-luciferase reporter assay were conducted to verify the binding between miR-223-3p and STK39. LPS-induced ALI mouse models were treated with BALF-exo loaded with miR-223-3p mimics. miR-223-3p was lowly expressed in BALF-exo from LPS-treated mice. BALF-exo loaded with miR-223-3p mimics increased viability and autophagy and decreased apoptosis and inflammation in NR8383 cell models. Inhibition of miR-223-3p in BALF-exo or overexpression of STK39 in NR8383 cells repressed the therapeutic effect of BALF-exo in LPS-treated NR8383 cells. STK39 was a target gene of miR-223-3p. miR-223-3p shuttled by BALF-exo negatively regulated the expression of STK39 in NR8383 cells. BALF-exo loaded with miR-223-3p mimics also reduced lung injuries in ALI mice. In conclusion, miR-223-3p loaded in BALF-exo alleviates ALI by targeting STK39 in alveolar macrophages.
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