2-Methoxyestradiol ameliorates paraquat-induced pulmonary fibrosis by inhibiting the TGF-β1/Smad2/3 signaling pathway

被引:1
作者
Hou, Linlin [1 ]
Yang, Fang [1 ]
Zhang, Yan [1 ]
Li, Yi [2 ]
Yan, Hongyi [1 ]
Meng, Cuicui [1 ]
Du, Yuqi [1 ]
Zhu, Huanzhou [1 ]
Yuan, Ding [1 ]
Gao, Yanxia [1 ]
机构
[1] Zhengzhou Univ, Emergency Dept, Med Key Lab Poisoning Dis Henan Prov, Affiliated Hosp 1, Zhengzhou 450000, Peoples R China
[2] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, State Key Lab Complex Severe & Rare Dis, Emergency Dept, Beijing 100000, Peoples R China
关键词
Paraquat poisoning; Pulmonary fibrosis; 2-Methoxyestradiol; INDUCED LUNG INJURY; MESENCHYMAL TRANSITION; OXIDATIVE STRESS; PROTECTS;
D O I
10.1016/j.pestbp.2023.105647
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Paraquat (PQ) is a highly effective and highly toxic herbicide that is highly toxic to both humans and animals. Pulmonary fibrosis is the primary cause of fatality in patients with PQ poisoning, there is no effective drug treatment yet. 2-Methoxyestradiol (2ME) is a natural metabolite of estradiol with anti-tumor, anti-angiogenesis, and anti-proliferative effects. Whether 2ME has the potential to inhibit pulmonary fibrosis induced by PQ is unclear. This study aims to investigate the potential effects and mechanism of 2ME on PQ-induced pulmonary fibrosis. C57BL/6 mice and A549 cells were exposed to PQ to establish pulmonary fibrosis model. In vivo, Hematoxylin and eosin (H&E) staining was utilized to assess the pathological characteristics. Masson's trichrome staining was employed to evaluate the collagen deposition. Western blot and immunohistochemistry were conducted to determine the expressions of fibrosis markers. In vitro, the expressions of epithelial-mesenchymal transition (EMT) markers were detected using western blot and immunofluorescence to evaluated the potential inhibition of PQ-induced EMT by 2ME. And proteins associated with the TGF-81/Smad2/3 signaling pathway were measured by western blot in vivo and in vitro. The result found that 2ME can ameliorated PQ-induced pulmonary fibrosis and inhibit the activation of TGF-81/Smad2/3 signaling pathway. These findings suggest that 2ME may serve as a potential therapeutic agent for treating PQ-induced pulmonary fibrosis.
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页数:10
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