AUTHOR=Chang Jing , Wang Jiahui , Luo Beibei , Li Weihao , Xiong Ziyue , Du Chaoqi , Wang Xue , Wang Yuejiao , Tian Jingya , Li Shuxin , Fang Yue , Li Longjie , Dong Jing , Tan Ke , Fan Yumei , Cao Pengxiu 

TITLE=Vitamin E stabilizes iron and mitochondrial metabolism in pulmonary fibrosis

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1240829

DOI=10.3389/fphar.2023.1240829

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> Pulmonary fibrosis (PF) is a fatal chronic lung disease that causes structural damage and decreased lung function and has a poor prognosis. Currently, there is no medicine that can truly cure PF. Vitamin E (VE) is a group of natural antioxidants with anticancer and antimutagenic properties. There have been a few reports about the attenuation of PF by VE in experimental animals, but the molecular mechanisms are not fully understood.</p><p><bold>Methods:</bold> Bleomycin-induced PF (BLM-PF) mouse model, and cultured mouse primary lung fibroblasts and MLE 12 cells were utilized. Pathological examination of lung sections, immunoblotting, immunofluorescent staining, and real-time PCR were conducted in this study.</p><p><bold>Results:</bold> We confirmed that VE significantly delayed the progression of BLM-PF and increased the survival rates of experimental mice with PF. VE suppressed the pathological activation and fibrotic differentiation of lung fibroblasts and epithelial-mesenchymal transition and alleviated the inflammatory response in BLM-induced fibrotic lungs and pulmonary epithelial cells <italic>in vitro</italic>. Importantly, VE reduced BLM-induced ferritin expression in fibrotic lungs, whereas VE did not exhibit iron chelation properties in fibroblasts or epithelial cells <italic>in vitro</italic>. Furthermore, VE protected against mitochondrial dysmorphology and normalized mitochondrial protein expression in BLM-PF lungs. Consistently, VE suppressed apoptosis in BLM-PF lungs and pulmonary epithelial cells <italic>in vitro</italic>.</p><p><bold>Discussion:</bold> Collectively, VE markedly inhibited BLM-induced PF through a complex mechanism, including improving iron metabolism and mitochondrial structure and function, mitigating inflammation, and decreasing the fibrotic functions of fibroblasts and epithelial cells. Therefore, VE presents a highly potential therapeutic against PF due to its multiple protective effects with few side effects.</p>