YAP-Induced Endothelial-Mesenchymal Transition in Oral Submucous Fibrosis
YAP-Induced Endothelial-Mesenchymal Transition in Oral Submucous Fibrosis
复制标题
YAP 诱导的口腔粘膜下纤维化内皮间质转化
DOI：
10.1177/0022034519851804
复制
发表时间：
2019-07-01
影响因子：
7.6
通讯作者：
Fang, C.
中科院分区：
文献类型：
--
作者：
Li, J.;Yao, M.;Fang, C.
口腔黏膜下纤维化（OSF）是一种潜在的恶性疾病。目前的研究表明，咀嚼槟榔被认为是OSF的主要原因，内皮-间充质转化（EndMT）参与了纤维化病变的发生和发展。然而，具体的分子机制和治疗方法尚不清楚。在这里，我们报道了槟榔碱诱导的EndMT的机制以及该机制在OSF中的重要性，我们还确定了降低OSF发病率的潜在治疗方法。我们证明了yes相关蛋白（YAP）在人类样本中的过表达，并且它与OSF的病理分期显著相关。槟榔碱通过增加活性氧水平和诱导PERK通路（真核翻译起始因子2 α激酶3）激活YAP，导致EndMT的起始并导致OSF。维替波芬是一种YAP-TEA通路抑制剂，可抑制EndMT，减少胶原积累，从而减轻小鼠OSF。这些数据表明槟榔碱调节YAP的活性，并强调了治疗OSF的另一种方法。
Oral submucous fibrosis (OSF) is a potentially malignant disorder. Current studies have shown that chewing areca nut is considered the main cause of OSF, and endothelial-mesenchymal transformation (EndMT) participates in the occurrence and development of the fibrotic lesion. However, the specific molecular mechanisms and treatments remain unclear. Here, we report the mechanism of arecoline-induced EndMT and the importance of this mechanism in OSF, and we also identify potential therapeutics for decreasing OSF incidence. We demonstrate the overexpression of Yes-associated protein (YAP) in human samples and that it was significantly associated with OSF pathologic stage. Arecoline activated YAP by increasing reactive oxygen species levels and inducing the PERK pathway (eukaryotic translation initiation factor 2 alpha kinase 3), resulting in the initiation of EndMT and leading to OSF. Verteporfin, a YAP-TEA domain pathway inhibitor, suppressed EndMT and decreased collagen accumulation, resulting in the alleviation of OSF in mice. These data indicate that arecoline regulates the activity of YAP and highlight an alternative method for treating OSF.