miR-18a-5p promotes phenotypic transformation of airway smooth muscle cells by targeting SPRY1 to activate the RAS-MAPK pathway.

OBJECTIVE: This study investigates the role of miR-18a-5p in the phenotypic transformation of airway smooth muscle cells (ASMCs) and its underlying mechanism in asthma-related airway remodeling. METHODS: Expression of miR-18a-5p in sputum from asthma patients was assessed by RT-qPCR. An in vitro model was established by stimulating ASMCs with TGF-β1. The responsiveness of miR-18a-5p expression to asthma-related mitogenic stimulation was also evaluated. ASMC proliferation and migration were evaluated following miR-18a-5p overexpression or inhibition using CCK-8 and Transwell assays. Western blot was used to detect migration-associated proteins, phenotypic markers and activation of the RAS-MAPK pathway. The regulatory relationship between miR-18a-5p and SPRY1 was validated by dual-luciferase assay, and SPRY1 knockdown was performed to explore its functional role. RESULTS: miR-18a-5p was significantly upregulated in asthma patients. Overexpression of miR-18a-5p promoted ASMC proliferation and migration, accompanied by upregulation of migration-related proteins (Integrin β1,p-FAK/FAK,p-Paxillin/Paxillin,MMP9), increased synthetic phenotype markers (α-SMA, OPN, Collagen I/III), and reduced contractile marker (Calponin). It also activated the RAS-MAPK pathway. SPRY1 was confirmed as a direct target of miR-18a-5p. Knockdown of SPRY1 reversed the effects of miR-18a-5p inhibition, confirming its role in mediating ASMC phenotypic changes. CONCLUSION: miR-18a-5p promotes ASMC phenotypic switching and airway remodeling in asthma by targeting SPRY1 and activating the RAS-MAPK signaling pathway. These findings suggest miR-18a-5p as a potential therapeutic target for asthma.