口腔黏膜下纤维化发生中基膜聚糖调控血管炎症的作用及潜在临床意义

Vascular inflammation is an early key pathological event of fibrosis diseases（Nature reviews, 2016）. Recently, the role of lumican in the process is increasingly concerned. Previous research identified over-expressed lumican is closely related to the development of oral submucous fibrosis(OSF). Besides, we found lumican was expressed highly in the vasculitis of early OSF. So our hypothesis is that lumican could play a important role in the occurrence of OSF through regulating vascular inflammation.To vertified that, firstly the regulation effect of lumican to vasculitis is studied by some methods such as immunohistochemistry, Western blot. And then, to evaluated the effects and potential mechanisms of vasculitis was modulated by lumican protein in the disease, we will adopt diverse techniques including lentiviral vector, cells co-cultured system,flow cytometry, Q-PCR, fibrosis animal models,. Finally, with nano-drug delivery systems, to investigate the possibility of silencing lumican could be one of targeted therapy of OSF. This study will reveal the important roles and molecular mechanism of lumican regulating vascular inflammation in the process of OSF, and provide substantial rationale for improving the current treatment model of OSF for tailored therapy.

血管炎是纤维化疾病早期关键病理事件（Nature reviews, 2016）。近年来，基膜聚糖在其中的作用受到日益关注，申请人发表的论文发现基膜聚糖的过表达与口腔黏膜下纤维化 （OSF）发生密切相关；还发现该蛋白在早期OSF血管炎症中表达增加，因此假定该蛋白可能通过调控血管炎症反应，促使OSF的发生。为验证此假说，首先，拟通过免疫组织化学、Q-PCR 等技术探讨基膜聚糖对OSF血管炎症的调控作用；然后，运用慢病毒载体、细胞共培养、流式细胞术、Western blot、纤维化动物模型等多种手段，综合评估基膜聚糖调控血管炎症在OSF发生中的重要作用，进一步发掘其具体的分子机制及相关调控网络；最后，结合纳米微粒药载系统探讨沉默基膜聚糖作为OSF靶向治疗的可能性。该研究将揭示OSF发生中基膜聚糖调控血管炎症的重要作用及分子机理，为改进口腔黏膜下纤维化现行诊疗模式，实现个体化治疗提供科学依据。

口腔黏膜下纤维化(oral submucous fibrosis，OSF)是常见的口腔潜在恶性疾患，其作为湖南地区高发疾病，驱动该病发生及发展的分子机制是本领域亟需解决的关键问题。前期课题组运用蛋白组学发现，基膜聚糖过表达与OSF发生密切相关，该蛋白分子在OSF的发生、发展中的作用受到了我们的关注。为此，首先我们探究了基膜聚糖在OSF发生、发展过程中的表达情况，并且统计相关的临床信息，对其临床意义进行初步的评估；然后，构建了细胞和纤维化动物模型，运用流式细胞术、细胞周期、Western blot、ELISA等多种手段，综合评估了在OSF发生和发展过程中的重要作用，为进一步发掘其具体的分子机制及相关调控网络提供依据；最后，构建了纳米微粒药载系统，探讨了其物理、化学及生物性能，为研究沉默基膜聚糖作为OSF靶向治疗提供可能性。该研究为揭示基膜聚糖在OSF发生、发展中的重要作用及分子机理提供了重要的理论依据，为改进口腔黏膜下纤维化现行诊疗模式，实现个体化治疗提供科学证据。