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