Midkine promotes PDGF-BB-induced proliferation, migration, and glycolysis of airway smooth muscle cells via the PI3K Akt pathway.

Airway smooth muscle cell (ASMC) dysfunction drives airway remodeling in asthma, yet the molecular mediators remain incompletely defined. Midkine, a pleiotropic growth factor, has emerged as a potential regulator of inflammatory and proliferative responses. This study investigated midkine expression and function in platelet-derived growth factor-BB (PDGF-BB)-stimulated ASMCs. Serum midkine levels were quantified in asthmatic children and healthy controls. Primary human ASMCs were stimulated with PDGF-BB and subjected to midkine knockdown using siRNA. Proliferation, migration, extracellular matrix (ECM) deposition, inflammatory cytokine production, glycolytic activity, and PI3K/Akt signaling were assessed using MTT, Transwell, RT-qPCR, ELISA, western blotting, and metabolic assays. Serum midkine levels were significantly elevated in patients with asthma. PDGF-BB stimulation increased midkine expression and ASMC proliferation, which were markedly suppressed by midkine silencing. Knockdown attenuated PDGF-BB-induced PI3K/Akt phosphorylation, reduced ASMC migration, and decreased collagen I and fibronectin expression levels. Midkine silencing also diminished TNF-α, IL-1β, and IL-6 production and lowered glucose consumption, lactate release, ATP generation, and the expression of PKM2 and LDHA. These findings indicate that midkine promotes ASMC proliferation, migration, inflammation, extracellular matrix deposition, and glycolysis via the PI3K/Akt signaling pathway, thereby contributing to airway remodeling in asthma.