From fibroblast foci to dense scars: PAK2-activated fibroblasts drive fibrosis progression in idiopathic pulmonary fibrosis

作者：Xuexi Zhang, Xue Liu, Paul W. Noble · 发表于：European Respiratory Journal · 年份：2025 · DOI：10.1183/13993003.01549-2025 · 被引用次数：4 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Lung Cancer Treatments and Mutations、Connective Tissue Growth Factor Research

Extract Fibrotic diseases contribute to nearly 45% of all deaths in the developed world, affecting vital organs such as the lungs, liver, heart and kidneys. Transforming growth factor (TGF)-β is a central driver of fibrosis, promoting the activation of fibroblasts into myofibroblasts and the excessive deposition of extracellular matrix [1]. The cell-type-specific activation of p21-activated kinase 2 (PAK2) in TGF-β signalling has been recognised for some time [2, 3], but its role in fibrotic diseases has only recently come to light [4]. With great interest, we read the recent article by W atanabe et al . [5], describing a novel cellular mechanism by which PAK2 may drive fibrotic remodelling and its implication for potential therapeutic targeting in idiopathic pulmonary fibrosis (IPF). This study offers valuable insights into the distinct fibroblast populations within fibroblastic foci (FF) and dense fibrosis (DF) regions of IPF through integrated spatial and single-cell transcriptomic analysis. The authors identify PAK2 as a key fibrogenic kinase activated in FF and surrounding areas, and demonstrate that its inhibition attenuates fibrosis in a murine model, suggesting PAK2 as a promising therapeutic target.