文献类型：期刊文献

英文题名：Antifibrotic Strategies Targeting Phosphodiesterase-4 in Idiopathic Pulmonary Fibrosis: Molecular Mechanisms and Clinical Translation

作者：Ma, Quan[1,2];Zhou, Shixin[3];Zhi, Xiaodong[3];Luo, Caifeng[4];Zhu, Zhongbo[1];Zhang, Xuhui[5];Liu, Xiping[1,6]

第一作者：马泉

通信作者：Zhang, XH[1];Liu, XP[2]

机构：[1]Gansu Univ Chinese Med, Sch Basic Med Sci, Lanzhou 730000, Peoples R China;[2]Gansu Univ Tradit Chinese Med, Affiliated Hosp, Dept Lung Dis, Lanzhou 730000, Peoples R China;[3]Gansu Univ Tradit Chinese Med, Coll Integrat Med, Lanzhou 730000, Peoples R China;[4]Gansu Univ Tradit Chinese Med, Gaolan Branch Hosp, Affiliated Hosp, Lanzhou 730200, Peoples R China;[5]Gansu Univ Tradit Chinese Med, Affiliated Hosp 3, Peoples Hosp Bai Yin City 1, Bai Yin 730900, Peoples R China;[6]Gansu Univ Tradit Chinese Med Lanzhou, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

通信机构：[1]corresponding author), Gansu Univ Tradit Chinese Med, Affiliated Hosp 3, Peoples Hosp Bai Yin City 1, Bai Yin 730900, Peoples R China;[2]corresponding author), Gansu Univ Tradit Chinese Med Lanzhou, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：18

外文期刊名：CLINICAL PHARMACOLOGY-ADVANCES AND APPLICATIONS

收录：WOS:【ESCI(收录号:WOS:001692298400001)】；

基金：Funding This work was supported by the National Natural Science Foundation of China (No.82260889) and the Natural Science Foundation of Gansu Province (No.24JRRD002) .

语种：英文

外文关键词：phosphodiesterase; phosphodiesterase 4 inhibitor; idiopathic pulmonary fibrosis; nerandomilast

摘要：Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterised by irreversible fibrosis of the lung parenchyma and a steady decline in respiratory function. Its pathogenesis remains incompletely understood, and despite advances in diagnosis and disease management, therapeutic options remain limited and largely palliative. Emerging evidence suggests that phosphodiesterase-4 (PDE4) inhibitors may represent a novel therapeutic approach in IPF through modulation of cyclic adenosine monophosphate-dependent signalling pathways. Preclinical and clinical studies indicate that PDE4 inhibition can attenuate key pathological processes implicated in IPF, including macrophage-driven inflammatory responses, dysregulated epithelial repair, and fibroblast proliferation and differentiation. Through these mechanisms, PDE4 inhibitors demonstrate combined anti-inflammatory and antifibrotic effects in experimental models of lung fibrosis. Among this class, the PDE4B-selective inhibitor nerandomilast has shown encouraging signals of efficacy in clinical trials of IPF, supporting continued investigation of subtype-selective targeting strategies. Other PDE4 inhibitors, including roflumilast, rolipram, and structurally novel derivatives such as 2-arylbenzofurans, have also demonstrated antifibrotic activity, predominantly in preclinical studies. This review synthesises current evidence on the role of PDE4 signalling in IPF pathogenesis and critically evaluates the pharmacological rationale, therapeutic potential, and translational challenges of PDE4 inhibitors in the treatment of IPF. Future perspectives, including subtype-selective inhibition and optimised drug delivery strategies, are discussed as potential avenues to improve efficacy and tolerability in this patient population.