1,25-Dihydroxyvitamin D3 attenuates TGF-β1-induced airway remodeling in asthma by inhibiting IL-33 mediated by the ERK1/2 signaling pathway

Airway remodeling is a central pathological feature of asthma, while 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) has known immunomodulatory and anti-fibrotic properties. And transforming growth factor-β1 (TGF-β1) plays a core role in inducing airway epithelial cells to transform into asthma model cells in vitro. However, the exact role and underlying mechanisms of 1,25(OH)₂D₃ in the context of TGF-β1-induced airway remodeling remain insufficiently elucidated. This study investigated the effects of 1,25(OH)₂D₃ on TGF-β1-induced airway remodeling using BEAS-2B and A549. TGF-β1 (5 ng/mL) induced pro-remodeling phenotypes, enhancing proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and fibrotic marker expression. 1,25(OH)₂D₃ (50 nM) effectively attenuated these changes. Mechanistically, TGF-β1 mediated effects through ERK1/2/IL-33 signaling pathway activation. 1,25(OH)₂D₃ exerted protective effects by inhibiting ERK1/2 phosphorylation, downregulating IL-33 expression. The study demonstrates that 1,25(OH)₂D₃ attenuates TGF-β1-induced airway remodeling through ERK1/2/IL-33 signaling modulation. And these findings provide new insights into the therapeutic potential of vitamin D in asthma and highlight its promise as a viable strategy for the prevention and management of airway remodeling.