Salvianolic Acid B Inhibited LH2 Expression to Reduce Collagen Synthesis in Pulmonary Fibrosis

Collagen deposition and scar formation are hallmark features of fibrotic diseases. Lysyl hydroxylase 2 (PLOD2/LH2), a key collagen-modifying enzyme, catalyses lysine hydroxylation at telopeptide sites to promote pyridinoline cross-link formation, thereby enhancing collagen stability and matrix stiffness. However, the mechanisms regulating LH2 in pulmonary fibrosis (PF) are not fully understood. Here, we identify Salvianolic acid B (SAB) as a potent antifibrotic compound that targets LH2-associated collagen cross-linking. LH2 expression was markedly increased in alveolar epithelial cells and fibroblasts during PF, and its silencing attenuated TGF-β1-induced fibrotic protein expression. SAB reduced LH2 protein levels and significantly alleviated fibrotic remodelling, as evidenced by restored lung architecture and reduced collagen deposition. Mechanistically, the antifibrotic effects of SAB and LH2 were associated with inhibition of epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transition (FMT), and the Wnt/β-catenin signalling pathway. This study indicates that pharmacological inhibition of LH2 by SAB effectively disrupts collagen cross-linking and fibrotic progression, offering a promising therapeutic avenue for pulmonary fibrosis.