博莱霉素
肺纤维化
特发性肺纤维化
纤维化
癌症研究
去铁胺
肌成纤维细胞
成纤维细胞
氧化应激
生物
免疫学
医学
肺
病理
细胞培养
内分泌学
内科学
生物化学
遗传学
化疗
作者
Zhuo Pei,Yifei Qin,Xianghui Fu,Fang Yang,Fei Huo,Xue Li,Shijie Wang,Hongyong Cui,Lin Peng,Gang Zhou,Jiangna Yan,Jiao Wu,Zhi‐Nan Chen,Ping Zhu
出处
期刊:Redox biology
[Elsevier]
日期:2022-11-01
卷期号:57: 102509-102509
被引量:38
标识
DOI:10.1016/j.redox.2022.102509
摘要
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease characterized by excessive proliferation of fibroblasts and excessive accumulation of extracellular matrix (ECM). Ferroptosis is a novel form of cell death characterized by the lethal accumulation of iron and lipid peroxidation, which is associated with many diseases. Our study addressed the potential role played by ferroptosis and iron accumulation in the progression of pulmonary fibrosis. We found that the inducers of pulmonary fibrosis and injury, namely, bleomycin (BLM) and lipopolysaccharide (LPS), induced ferroptosis of lung epithelial cells. Both the ferroptosis inhibitor liproxstatin-1 (Lip-1) and the iron chelator deferoxamine (DFO) alleviated the symptoms of pulmonary fibrosis induced by bleomycin or LPS. TGF-β stimulation upregulated the expression of transferrin receptor protein 1 (TFRC) in the human lung fibroblast cell line (MRC-5) and mouse primary lung fibroblasts, resulting in increased intracellular Fe2+, which promoted the transformation of fibroblasts into myofibroblasts. Mechanistically, TGF-β enhanced the expression and nuclear localization of the transcriptional coactivator tafazzin (TAZ), which combined with the transcription factor TEA domain protein (TEAD)-4 to promote the transcription of TFRC. In addition, elevated Fe2+ failed to induce the ferroptosis of fibroblasts, which might be related to the regulation of iron export and lipid metabolism. Finally, we specifically knocked out TFRC expression in fibroblasts in mice, and compared with those in the control mice, the symptoms of pulmonary fibrosis were reduced in the knockout mice after bleomycin induction. Collectively, these findings suggest the therapeutic potential of ferroptosis inhibitors and iron chelators in treating pulmonary fibrosis.
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