Li Weiyi, Xie Yinghai, Chen Zhenzhen, Cao Dongli, Wang Yu
School of Medicine, Anhui University of Science and Technology, Huainan, China.
Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Huainan, China.
Front Med (Lausanne). 2025 Sep 8;12:1658001. doi: 10.3389/fmed.2025.1658001. eCollection 2025.
Pulmonary fibrosis is a progressive lung-scarring disease for which curative options remain limited. This review examines how epithelial-mesenchymal transition (EMT) contributes to fibrotic remodeling in subsets of pulmonary fibrosis (PF), delineates where the evidence is strongest, and highlights emerging therapeutic directions. PF encompasses idiopathic PF (IPF) and diverse non-IPF interstitial lung diseases driven by autoimmunity, exposures, or genetics, in which EMT involvement is variable. Recent laboratory and clinical work has been analyzed and the evidence grouped into four areas: well-known growth-factor signals; immune and inflammatory crosstalk; newer drivers such as iron-linked cell death, metabolic change and tissue stretch; and emerging medicines that temper these pathways, including licensed antifibrotics, experimental small molecules, natural compounds and RNA-based agents. Collectively, EMT emerges as a potentially reversible hub linking epithelial stress to scar formation, suggesting stage-specific combination strategies supported by single-cell profiling, lung organoids, and targeted delivery.
肺纤维化是一种进行性肺瘢痕形成疾病,目前的治疗选择仍然有限。本综述探讨上皮-间质转化(EMT)如何在部分肺纤维化(PF)亚型中促成纤维化重塑,明确证据最确凿的领域,并突出新兴的治疗方向。PF包括特发性PF(IPF)以及由自身免疫、暴露或遗传因素驱动的多种非IPF间质性肺疾病,其中EMT的参与情况各不相同。近期的实验室和临床研究已被分析,证据被归为四个领域:知名的生长因子信号;免疫和炎症相互作用;铁相关细胞死亡、代谢变化和组织拉伸等新的驱动因素;以及调节这些途径的新兴药物,包括已获许可的抗纤维化药物、实验性小分子、天然化合物和基于RNA的药物。总体而言,EMT成为一个潜在的可逆枢纽,将上皮应激与瘢痕形成联系起来,这表明由单细胞分析、肺类器官和靶向递送支持的阶段特异性联合策略。