TGFβ1介导的整合素α1/α2在牙龈增生性疾病中的作用

Gingival overgrowth (GO) is mainly caused by drug therapy (drug-induced gingival overgrowth, DIGO) and hereditary factors (hereditary gingival overgrowth, HGF). The excessive accumulation of collagen typeⅠis the most prominent pathologic feature of this disease. However, it is not well established about the mechanism of collagen accumulation in DIGO and HGF. The study aims to clarify the pathogenic mechanisms potentially involved. Gingival tissues and fibroblasts from healthy objects, HGF patients, and DIGO patients are included in this study. Firstly, to identify the coexistence of integrinα1/α2 and TGFβ1 signialing in gingive, we will use immunofluorescence technique to detect the expression of integrinα1/α2 and TGFβ1R in both gingival tissues and fibroblasts. Secondly, to clarify the possible roles of integrinα1/α2 in GO fibroblasts, the expression of integrinα1/α2 in three different types of cells will be increased or inhibited by viral transduction technology. Then, cell cycle, cell phagocytic ability of collagen typeⅠ，and the expression of collagen typeⅠ metabolism related cytokines and related pathway factor in cells will be detected and compared. Thirdly, the role of TGFβ1 mediated integrin α1/α2 will be detected.

牙龈增生性疾病主要包括遗传性牙龈纤维瘤病（HGF）和药物性牙龈增生（DIGO），其最显著的病理特点是是Ⅰ型胶原的大量堆积，导致胶原堆积的分子机制不同而且尚不明确。本研究以来源于正常人、HGF和DIGO的组织以及牙龈成纤维细胞为研究对象，利用免疫荧光技术检测整合素α1/α2和TGFβ1R在牙龈组织和成纤维细胞中的表达，从而明确α1/α2与TGFβ1信号通路的共存性。另外，采用病毒转导技术分别使整合素α1/α2在三组细胞中的过表达和抑制表达，通过检测和比较各组细胞周期、细胞吞噬Ⅰ型胶原的能力以及胶原代谢相关因子和相关通路因子在各组细胞中的表达水平，从而探讨整合素α1/α2在牙龈增生性疾病中可能发挥的作用，寻求导致HGF和DIGO胶原堆积的主要原因和不同之处。此外，通过检测TGFβ1对整合素α1/α2的调控作用，探讨TGFβ1介导的整合素α1/α2在牙龈增生性疾病中所发挥的作用。

药物性牙龈增生（DIGO），其最显著的病理特点是是Ⅰ型胶原的大量堆积，导致胶原堆积的分子机制不同而且尚不明确。本研究以来源于正常人和DIGO的组织以及牙龈成纤维细胞为研究对象，利用免疫组化技术检测整合素α1/α2和TGFβ1R在牙龈组织和成纤维细胞中的表达，研究整合素α1/α2与药物性牙龈增生的关系。原代培养DIGO组织细胞，并建立更接近组织环境的三维培养模型，研究在三维环境下，DIGO源细胞内整合素α1/α2的变化。探讨DIGO与两种整合素α1/α2的关系。