Polyhexamethylene guanidine aerosol triggers pulmonary fibrosis concomitant with elevated surface tension via inhibiting pulmonary surfactant
Polyhexamethylene guanidine aerosol triggers pulmonary fibrosis concomitant with elevated surface tension via inhibiting pulmonary surfactant
复制标题
聚六亚甲基胍气雾剂通过抑制肺表面活性物质引发肺纤维化并伴有表面张力升高
DOI：
10.1016/j.jhazmat.2021.126642
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发表时间：
2021-07-20
影响因子：
13.6
通讯作者：
Tang, Jinglong
中科院分区：
文献类型：
--
作者：
Li, Xin;Zhang, Jianzhong;Tang, Jinglong
环境化学物质吸入暴露可诱发肺纤维化，其特征是成纤维细胞过度增殖和细胞外基质成分积累，其中表面张力通常起重要作用。聚六亚甲基胍（PHMG）首次被确认为加湿器消毒剂的潜在危险成分，并在韩国引发了肺纤维化疫情。然而，phmg诱导的肺纤维化的潜在机制尚未完全阐明。因此，本研究主要关注PHMG对表面张力的影响，揭示PHMG诱导肺纤维化的影响及其机制。C57BL/6J小鼠暴露于亚急性PHMG气溶胶8周。结果表明，PHMG诱导肺纤维化并伴有表面张力升高。体外实验结果进一步证实了PHMG通过抑制肺表面活性物质提高表面张力。机制上，PHMG通过抑制关键表面活性剂蛋白SP-B和SP-C的表达，阻断其活性位点，从而抑制其活性。本研究首次揭示了基于肺表面活性物质抑制介导的表面张力升高的phmg诱导肺纤维化的分子机制。肺表面活性物质可能是进一步干预的潜在靶点，以预防phmg诱导的纤维化或缓解相关患者的症状。
Environmental chemicals inhalation exposure could induce pulmonary fibrosis, which is characterized by the excessive proliferation of fibroblasts and accumulation of extracellular matrix components, in which surface tension usually plays vital roles. Polyhexamethylene guanidine (PHMG) was first recognized as a potential hazard ingredient in humidifier disinfectants, which caused an outbreak of pulmonary fibrosis in South Korea. However, the underlying mechanisms involved in PHMG-induced pulmonary fibrosis have not yet been fully elucidated. Therefore, this study mainly focuses on the effect of PHMG on surface tension to unveil the influence and involved mechanisms in PHMG-induced pulmonary fibrosis. C57BL/6J mice were exposed to sub-acute PHMG aerosol for 8 weeks. The results indicated that PHMG induced pulmonary fibrosis combined with elevated surface tension. Results from in vitro study further confirmed PHMG elevated surface tension by inhibited pulmonary surfactant. Mechanistically, PHMG suppressed the key surfactant protein SP-B and SP-C by inhibiting protein expression and block their active sites. The present study, for the first time, revealed the molecular mechanism of PHMG-induced pulmonary fibrosis based on pulmonary surfactant inhibition mediated surface tension elevated. And pulmonary surfactant may be a potential target for further intervention to prevent PHMG-induced fibrosis or alleviate the symptom of relevant patients.