Programa de Pós-Graduação em Ciências Biológicas, Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Department of Periodontology, Institute of Dentistry, University of Turku, Turku, Finland.
J Periodontal Res. 2018 Oct;53(5):916-923. doi: 10.1111/jre.12583. Epub 2018 Jul 4.
Elevated levels of matrix metalloproteinase-7 (MMP7) have been observed in serum samples of subjects with type 2 diabetes mellitus (T2DM) and in gingival tissues of subjects with periodontitis. The aim of the present study was to collect in vivo and in silico evidence on the role of MMP7 in the interplay between T2DM and generalized periodontitis (GP).
The extent of MMP7 expression and localization were immunohistochemically analyzed in gingival tissues of patients with GP with T2DM (T2DM/GP, n = 11), systemically healthy patients with GP (n = 7), and systemically and periodontally healthy controls (n = 11). An in silico network model was built to determine the interactions between MMP7 and T2DM pathways. Regulation of neutrophil transmigration by MMP7 was analyzed in a knock-out mice model.
In human gingival tissues, the proportion of cells with robust MMP7 expression was elevated in patients with T2DM/GP in comparison to controls (P = .014). According to the in silico analysis, "hydroxyl radical" and "hydrogen peroxide" compounds were among the most central nodes of the network, and were within the shortest paths connecting "glucose" to "MMP7." In MMP7 knock-out mice, an intense accumulation of neutrophils was observed in the gingival epithelium as compared to wild-type mice (P = .0001).
Elevated MMP7 expression in gingival tissues of patients with T2DM/GP is related to the activation of reactive oxygen species by hyperglycemia. Suppression of MMP7 expression results in impaired neutrophil transmigration in gingiva.
在 2 型糖尿病（T2DM）患者的血清样本和牙周炎患者的牙龈组织中，均观察到基质金属蛋白酶-7（MMP7）水平升高。本研究旨在收集 MMP7 在 T2DM 与广泛性牙周炎（GP）相互作用中的体内和计算机模拟证据。
采用免疫组织化学方法分析了伴有 T2DM 的 GP（T2DM/GP，n=11）、系统健康的 GP 患者（n=7）和系统及牙周健康对照者（n=11）的牙龈组织中 MMP7 的表达和定位程度。构建了一个计算机模拟网络模型，以确定 MMP7 与 T2DM 途径之间的相互作用。在敲除小鼠模型中分析了 MMP7 对中性粒细胞迁移的调节作用。
与对照组相比，T2DM/GP 患者的牙龈组织中具有强 MMP7 表达的细胞比例升高（P=0.014）。根据计算机模拟分析，“羟自由基”和“过氧化氢”化合物是网络中最核心的节点之一，并且是连接“葡萄糖”与“MMP7”的最短路径内的节点。在 MMP7 敲除小鼠中，与野生型小鼠相比，牙龈上皮中观察到大量中性粒细胞积聚（P=0.0001）。
T2DM/GP 患者牙龈组织中 MMP7 表达升高与高血糖引起的活性氧物质激活有关。抑制 MMP7 表达会导致牙龈中中性粒细胞迁移受损。
