Melatonin Protects against Lung Fibrosis by Regulating the Hippo/YAP Pathway.
Melatonin Protects against Lung Fibrosis by Regulating the Hippo/YAP Pathway.
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褪黑素通过调节 Hippo/YAP 通路预防肺纤维化
DOI：
10.3390/ijms19041118
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发表时间：
2018-04-09
影响因子：
5.6
通讯作者：
Liang H
中科院分区：
文献类型：
--
作者：
Zhao X;Sun J;Su W;Shan H;Zhang B;Wang Y;Shabanova A;Shan H;Liang H
特发性肺纤维化（IPF）是一种进行性纤维化间质性肺炎，死亡率高。褪黑激素是一种主要由松果体分泌的激素，据报道参与了IPF的过程。然而，褪黑激素在肺纤维化中的作用机制至今尚未阐明。本研究旨在探讨褪黑素在肺纤维化中的抗纤维化作用及其机制。我们观察到褪黑激素显著减轻博莱霉素（BLM）诱导的小鼠实验性肺纤维化，并抑制TGF-β1诱导的肺成纤维细胞的纤维化。此外，我们还确定了褪黑激素受体抑制剂luzindole降低了褪黑激素的抗纤维化作用。进一步的研究表明，褪黑激素通过与其受体相互作用，在体内和体外减轻了YAP 1从细胞质到细胞核的移位，YAP 1是Hippo通路的关键下游效应子。总之，我们的研究结果表明，褪黑激素通过抑制YAP 1来预防肺纤维化，并表明褪黑激素替代可能是治疗肺纤维化的新策略。
Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic interstitial pneumonia with high mortality. Melatonin, a hormone predominantly secreted by the pineal gland, has been reported to participate in the process of IPF. However, the mechanisms underlying the effect of melatonin in pulmonary fibrosis have not been elucidated to date. This study was designed to evaluate the anti-fibrotic role of melatonin in pulmonary fibrosis and to elucidate the potential mechanisms. We observed that melatonin markedly attenuated bleomycin (BLM)-induced experimental lung fibrosis in mice and inhibited TGF-β1-induced fibrogenesis in lung fibroblasts. Additionally, we determined that luzindole, a melatonin receptor inhibitor, reduced the anti-fibrotic effect of melatonin. Further studies showed that melatonin alleviated the translocation of YAP1 from cytoplasm to nucleus, a key downstream effector of the Hippo pathway, in vivo and in vitro by interacting with its receptor. Taken together, our results suggest that melatonin prevents lung fibrosis by inhibiting YAP1 and indicate that melatonin replacement could be a novel strategy for the treatment of lung fibrosis.
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DOI：
10.5935/1984-0063.20170003
发表时间：
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期刊：
Sleep science (Sao Paulo, Brazil)
影响因子：
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