口腔粘膜下纤维性变(OSF)属口腔癌前病变,咀嚼槟榔是致病的主要因素,但其致病机制并不明确。有关Notch与纤维化的研究表明Notch信号通路与肺脏、肾脏、肝脏、心肌及系统性硬化病等的纤维化形成密切相关。目前,有关Notch信号通路在OSF发生发展中的作用及机制鲜有报道。本课题组在前期工作中发现Notch信号通路与口腔鳞癌的侵袭和转移关系密切。OSF属癌前病变，我们推测Notch信号通路是否也在其发生发展中起关键作用。本项目拟从临床组织,动物模型,细胞水平三个层次阐述Notch信号通路与OSF的关系,采用分子细胞生物学实验方法检测Notch信号通路相关分子在OSF组织细胞的表达情况,并上调或抑制其关键信号基因来干预Notch通路,探讨其与OSF的关系,为开发抗OSF药物提供新的分子靶点,为临床提供理论及治疗的新思路。

Oral submucous fibrosis (OSF) is the oral precancer condition, mainly caused by chewing areca nut, but, the underlying mechanism is still unclear. Studies of notch cascade and fibrosis indicated that the notch cascade is closely related with multi-organ fibrosis including lung, kidney, liver, myocardium, and systemic sclerosis. However, researches on the role of notch cascade in OSF is seldom reported. Our previous studies showed that notch cascade plays important role in the transfer and invasion progress of oral squamous cell carcinomas. OSF is one of the oral precancer conditions, we hypothesize that notch cascade may be also involved in the development and progression of OSF. This subject aims to find the relationship between notch cascade and OSF from three aspects: clinical tissue, animal mode and primary culture cells. In this subject, we will use molecular cell biology methods to detect the genes and proteins expression of notch cascade related molecules in the OSF tissue and cells, furthermore, we will observe the effects of intervention of notch cascade on OSF by upregulating or blocking the notch cascade, This subject will provide a new molecular target and a new therpeutic strategy in the preventment and treatment of OSF.