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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HN and LHX conceived the ideas. HN and LHX designed the experiments. THY, DXY and LHX performed the experiments. LHX and THY analyzed the data. HN and THY provided critical materials. DXY and SL wrote the manuscript. HN supervised the study. HN, LHX and QB revised the manuscript. All the authors have read and approved the final version for publication.
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All animal experiments were approved by the Animal Care and Use Committee of The Second Xiangya Hospital of Central South University and abided by the guidelines for laboratory animal care and use issued by the National Institutes of Health. Additionally, all the experiments were carried out with the best efforts to reduce the pain and number of experimental animals.
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He, N., Tan, H., Deng, X. et al. MiR-223-3p-loaded exosomes from bronchoalveolar lavage fluid promote alveolar macrophage autophagy and reduce acute lung injury by inhibiting the expression of STK39. Human Cell 35, 1736–1751 (2022). https://doi.org/10.1007/s13577-022-00762-w
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DOI: https://doi.org/10.1007/s13577-022-00762-w