Idiopathic pulmonary fibrosis microenvironment: Novel mechanisms and research directions

作者：Fuguo Gao, Lei Pan, Wei Liu, Jian Chen, Yifeng Wang, Yan Li, Yurou Liu, Yiying Hua, Ruiqi Li, Tongtong Zhang, Ting Zhu, Faguang Jin, Yongheng Gao · 发表于：International Immunopharmacology · 年份：2025 · DOI：10.1016/j.intimp.2025.114653 · 被引用次数：26 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Inhalation and Respiratory Drug Delivery、Extracellular vesicles in disease

Idiopathic Pulmonary Fibrosis (IPF) is a progressive interstitial lung disease marked by increasing dyspnea and respiratory failure. The underlying mechanisms remain poorly understood, given the complexity of its pathogenesis. This review investigates the microenvironment of IPF to identify novel mechanisms and therapeutic avenues. Studies have revealed that various cell types, including alveolar epithelial cells, fibroblasts, myofibroblasts, and immune cells, are integral to disease progression, engaging in cellular stress responses and inflammatory regulation via signaling pathways such as TGF-β, Wnt, mTOR, and ROS. Non-coding RNAs, particularly miRNAs, are critical in IPF and may serve as diagnostic and prognostic biomarkers. Regarding treatment, mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) or non-vesicular derivatives offer promise by modulating immune responses, enhancing tissue repair, and inhibiting fibrosis. Additionally, alterations in the lung microbiota are increasingly recognized as a contributing factor to IPF progression, offering fresh insights into potential treatments. Despite the encouraging results of MSC-based therapies, the precise mechanisms and clinical applications remain subjects of ongoing research. This review emphasizes the significance of the IPF microenvironment and highlights the need for further exploration to develop effective therapies that could enhance patient outcomes. • This review explores the complex microenviron...