Gao Fuguo, Pan Lei, Liu Wei, Chen Jian, Wang Yifeng, Li Yan, Liu Yurou, Hua Yiying, Li Ruiqi, Zhang Tongtong, Zhu Ting, Jin Faguang, Gao Yongheng
Department of Pulmonary and Critical Care Medicine, Tangdu hospital, Air Force Medical University, Xi'an, 710038, China.
Department of Pulmonary and Critical Care Medicine, Tangdu hospital, Air Force Medical University, Xi'an, 710038, China; Department of Pulmonary and Critical Care Medicine, Shaanxi provincal people's hospital, Xi'an, 710068, China.
Int Immunopharmacol. 2025 May 16;155:114653. doi: 10.1016/j.intimp.2025.114653. Epub 2025 Apr 13.
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.
特发性肺纤维化（IPF）是一种进行性间质性肺疾病，其特征为呼吸困难和呼吸衰竭不断加重。鉴于其发病机制的复杂性，其潜在机制仍知之甚少。本综述旨在研究IPF的微环境，以确定新的机制和治疗途径。研究表明，包括肺泡上皮细胞、成纤维细胞、肌成纤维细胞和免疫细胞在内的多种细胞类型对疾病进展至关重要，它们通过TGF-β、Wnt、mTOR和ROS等信号通路参与细胞应激反应和炎症调节。非编码RNA，尤其是微小RNA（miRNA），在IPF中起着关键作用，可能作为诊断和预后生物标志物。在治疗方面，间充质干细胞（MSC）及其细胞外囊泡（EV）或非囊泡衍生物有望通过调节免疫反应、促进组织修复和抑制纤维化发挥作用。此外，肺部微生物群的改变越来越被认为是IPF进展的一个促成因素，为潜在治疗提供了新的见解。尽管基于MSC的疗法取得了令人鼓舞的结果，但其确切机制和临床应用仍是正在进行的研究课题。本综述强调了IPF微环境的重要性，并强调需要进一步探索以开发能够改善患者预后的有效疗法。
