Pulmonary fibrosis (PF) is a fatal and irreversible respiratory disease accompanied by excessive fibroblast activation. Previous studies have suggested that cAMP signaling pathway and cGMP-PKG signaling pathway are continuously down-regulated in lung fibrosis, whereas PDE10A has a specifically expression in fibroblasts/myofibroblasts in lung fibrosis. In this study, we demonstrated that overexpression of PDE10A induces myofibroblast differentiation, and papaverine, as a PDE10A inhibitor used for vasodilation, inhibits myofibroblast differentiation in human fibroblasts, Meanwhile, papaverine alleviated bleomycin-induced pulmonary fibrosis and amiodarone-induced oxidative stress, papaverine downregulated VASP/β-catenin pathway to reduce the myofibroblast differentiation. Our results first demonstrated that papaverine inhibits TGFβ1-induced myofibroblast differentiation and lung fibrosis by VASP/β-catenin pathway.

肺纤维化 (PF) 是一种致命且不可逆转的呼吸系统疾病，伴有成纤维细胞过度活化。既往研究表明cAMP信号通路和cGMP-PKG信号通路在肺纤维化过程中持续下调，而PDE10A在肺纤维化过程中在成纤维细胞/肌成纤维细胞中特异性表达。在这项研究中，我们证明了 PDE10A 的过表达诱导肌成纤维细胞分化，罂粟碱作为 PDE10A 抑制剂用于血管舒张，抑制人成纤维细胞中的肌成纤维细胞分化，同时，罂粟碱减轻博来霉素诱导的肺纤维化和胺碘酮诱导的氧化应激，罂粟碱下调VASP/β-连环蛋白通路减少肌成纤维细胞分化。