Melatonin Protects against Lung Fibrosis by Regulating the Hippo/YAP Pathway

作者:Zhao, Xiaoguang; Sun, Jian; Su, Wei; Shan, Huitong; Zhang, Bowen; Wang, Yining; Shabanova, Azaliia; Shan, Hongli; Liang, Haihai*
来源:International Journal of Molecular Sciences, 2018, 19(4): 1118.
DOI:10.3390/ijms19041118

摘要

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-beta 1-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.