SPP1 regulates alveolar type 2 cell-macrophage cross talk and epithelial cell fate in iron-driven lung fibrosis

作者：Xinqian Du, Xinyu Zhang, Zhe Wang, Dan Wang, Yunqi Li, Zengqing Liu, Qing Miao, Hanxiao Zhang, Luo Duan, Yue Hu, Muzhi Zhang, Jie Liu, Zhe Lv, Yan Chen, Wei Wang, Ying Sun, Ye Cui · 发表于：American Journal of Physiology-Cell Physiology · 年份：2025 · DOI：10.1152/ajpcell.00140.2025 · 被引用次数：5 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Iron Metabolism and Disorders、Extracellular vesicles in disease

This study reveals a novel mechanism linking iron dysregulation to pulmonary fibrosis through SPP1-mediated reprogramming of alveolar type 2 cells. We demonstrate SPP1’s dual role: externally coordinating macrophage recruitment and internally directing pathological epithelial transitions toward a Krt8 + intermediate state. These findings, validated across multiple mouse models and human specimens, identify the SPP1 signaling axis as a promising therapeutic target, offering new hope for treating this devastating condition where treatment options have historically been limited.