J Immunol. 2026 Apr 15;215(4):vkaf376. doi: 10.1093/jimmun/vkaf376.
ABSTRACT
This study investigated the protective effect of miR-449b-5p from adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exos) targeting type 1 insulin-like growth factor receptor (IGF1R) on airway smooth muscle cells (ASMCs) and further investigated its mechanism of action. ADSC-Exos were isolated and characterized. Cellular uptake of ADSC-Exos by ASMCs was observed. Differences in serum miR-449b-5p expression levels between healthy children and asthmatic children were detected by RT-qPCR. The possible binding sites of miR-449b-5p and IGF1R were identified and then verified. The proliferation of ASMCs was determined by MTT assay and EdU assay. Cell cycle of ASMCs was measured by flow cytometry. Cell contraction of ASMCs was evaluated by inverted microscopy. IL-4, IL-5, and IFN-γ were measured by ELISA to evaluate the inflammatory response of ASMCs. ADSC-Exos exerted therapeutic effects on ASMCs by effectively inhibiting proliferation, cell contraction, and inflammatory response. miR-449b-5p upregulation in ASMCs effectively inhibited the promoting effect of PDGF-BB on cellular proliferation and contraction, while IGF1R upregulation showed the opposite effect. miR-449b-5p in ADSC-Exos targeted IGF1R to alleviate airway inflammation in asthma and improve ASMC dysfunction. ADSC-Exos carrying miR-449b-5p improve ASMC dysfunction, excessive proliferation, and inflammatory responses by downregulating IGF1R.
PMID:41986878 | DOI:10.1093/jimmun/vkaf376