Iron-laden macrophage-mediated paracrine profibrotic signaling induces lung fibroblast activation

作者：Yunqi Li, Xinqian Du, Yue Hu, Dan Wang, Luo Duan, Hanxiao Zhang, Ruoyang Zhang, Yingjie Xu, Ruonan Zhou, Xinyu Zhang, 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：2024 · DOI：10.1152/ajpcell.00675.2023 · 被引用次数：20 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Extracellular vesicles in disease、Pulmonary Hypertension Research and Treatments

This study investigates the role of iron in pulmonary fibrosis, specifically focusing on macrophage-mediated mechanisms. Iron accumulation in fibrotic lung macrophages triggers lipid peroxidation and an upregulation of transforming growth factor (TGF)-β1 expression. Coculturing iron-laden macrophages activates lung fibroblasts in a TGF-β1-dependent manner, which can be mitigated by ferroptosis inhibitors. These findings underscore the potential of targeting iron overload and lipid peroxidation as a promising strategy to alleviate fibrotic stimulation provoked by disease-associated macrophages.