NecroX-5 通过抑制 NLRP3 介导体上皮-间充质转化缓解博来霉素诱导的肺纤维化。
NecroX-5 ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3-mediated epithelial-mesenchymal transition.
机构信息
Department of Pain Management, Wuhan First Hospital, Wuhan, China.
Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
出版信息
Respir Res. 2022 May 20;23(1):128. doi: 10.1186/s12931-022-02044-3.
BACKGROUND
Pulmonary fibrosis is a progressive and usually lethal pulmonary disease. Despite considerable research efforts, no effective therapeutic strategy for pulmonary fibrosis has been developed. NecroX-5 has been reported to possess anti-inflammatory, anti-oxidative and anti-tumor activities. In the present study, we aimed to determine whether NecroX-5 exhibits antifibrotic property in bleomycin (BLM)-induced pulmonary fibrosis.
RESULTS
We found that pre-treatment with NecroX-5 alleviated inflammatory response, reduced oxidative stress, inhibited epithelial-mesenchymal transition (EMT), and ameliorated pulmonary fibrosis in vivo and in vitro. Our data further indicated that NecroX-5 substantially reduced activation of NLRP3 inflammasome and TGF-β1/Smad2/3 signaling in vivo and in vitro. Additionally, NLRP3 overexpression significantly reversed the protective effects of NecroX-5 in lung epithelial cells exposed to BLM.
CONCLUSIONS
Overall, our results demonstrate the potent antifibrotic properties of NecroX-5 and its therapeutic potential for pulmonary fibrosis.
背景
肺纤维化是一种进行性且通常致命的肺部疾病。尽管进行了大量的研究工作，但尚未开发出针对肺纤维化的有效治疗策略。NecroX-5 已被报道具有抗炎、抗氧化和抗肿瘤活性。在本研究中，我们旨在确定 NecroX-5 是否在博来霉素（BLM）诱导的肺纤维化中表现出抗纤维化特性。
结果
我们发现，NecroX-5 的预处理减轻了炎症反应，减少了氧化应激，抑制了上皮-间充质转化（EMT），并改善了体内和体外的肺纤维化。我们的数据进一步表明，NecroX-5 可显著减少体内和体外 NLRP3 炎性小体和 TGF-β1/Smad2/3 信号通路的激活。此外，NLRP3 的过表达显著逆转了 NecroX-5 在暴露于 BLM 的肺上皮细胞中的保护作用。
结论
总体而言，我们的结果表明 NecroX-5 具有强大的抗纤维化特性及其治疗肺纤维化的潜力。
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