Table 2_Adipose-derived mesenchymal stem cell-exosomes attenuate lipopolysaccharide-induced acute lung injury in mice by regulating the TGFBR2/Smad4 axis to suppress NLRP3-mediated macrophage M1 polarization and pyroptosis.docx

The expression of miR-19b-3p, TGFBR2, mothers against decapentaplegic homolog 4 (Smad4), and NOD-like receptor protein 3 (NLRP3), together with macrophage polarization, pyroptosis, and epithelial cell apoptosis, was assessed. Predicted molecular interactions were validated using bioinformatic analyses and the JASPAR database.</p>Results<p>ADMSC-Exo alleviated LPS-induced lung injury by preserving alveolar architecture and reducing lung injury scores and the W/D ratio.

They inhibited M1 macrophage polarization and pyroptosis both in vivo and in vitro, thereby decreasing apoptosis of lung epithelial cells. Mechanistically, ADMSC-Exo-delivered miR-19b-3p, which targeted TGFBR2 and inhibited TGFBR2/Smad4 signaling, resulting in transcriptional suppression of NLRP3 expression. Inhibition of miR-19b-3p or overexpression of Smad4/NLRP3 partially abolished the protective effects of ADMSC-Exo.

Collectively, ADMSC-Exo attenuated LPS-induced ALI by suppressing NLRP3-mediated macrophage M1 polarization and pyroptosis through the miR-19b-3p/TGFBR2/Smad4 signaling axis.</p>Conclusion<p>ADMSC-derived exosomes alleviate LPS-induced acute lung injury by delivering miR-19b-3p to inhibit the TGFBR2/Smad4 signaling pathway, thereby suppressing NLRP3-mediated macrophage M1 polarization and pyroptosis and reducing lung epithelial cell apoptosis.</p>