Background
Obstructive sleep apnea hypopnea syndrome (OSAHS) is an underestimated sleep disorder that leads to multiple organ damages, including lung injury (LI). This paper sought to analyze the molecular mechanism of extracellular vesicles (EVs) from adipose-derived mesenchymal stem cells (ADSCs) in OSAHS-induced lung injury (LI) via the miR-22-3p/histone lysine demethylase 6 B (KDM6B)/high mobility group AT-hook 2 (HMGA2) axis.
Conclusion
ADSCs-EVs transferred miR-22-3p to pneumonocytes and reduced apoptosis, inflammation, and oxidative stress through KDM6B/HMGA2, mitigating OSAHS-LI progression.
Methods
ADSCs and ADSCs-EVs were separated and characterized. Chronic intermittent hypoxia (CIH) was used to mimic OSAHS-LI, followed by ADSCs-EVs treatment and hematoxylin and eosin staining, TUNEL, ELISA, and assays of inflammation and oxidative stress (MPO/ROS/MDA/SOD). The CIH cell model was established and treated with ADSCs-EVs. Cell injury was assessed by the assays of MTT, TUNEL, ELISA, and others. Levels of miR-22-3p, KDM6B, histone H3 trimethylation at lysine 27 (H3K27me3), and HMGA2 were determine by RT-qPCR or Western blot analysis. The transfer of miR-22-3p by ADSCs-EVs was observed by fluorescence microscopy. Gene interactions were analyzed by dual-luciferase assay or chromatin immunoprecipitation.
Results
ADSCs-EVs effectively alleviated OSAHS-LI by reducing lung tissue injury, apoptosis, oxidative stress, and inflammation. In vitro, ADSCs-EVs increased cell viability and reduced apoptosis, inflammation and oxidative stress. ADSCs-EVs delivered enveloped miR-22-3p into pneumonocytes to upregulate miR-22-3p expression, inhibit KDM6B expression, increase H3K27me3 levels on the HMGA2 promoter, and decrease HMGA2 mRNA levels. Overexpression of KDM6B or HMGA2 attenuated the protective role of ADSCs-EVs in OSAHS-LI.