Regulation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases by Porphyromonas gingivaiis in an engineered human oral mucosa model
Regulation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases by Porphyromonas gingivaiis in an engineered human oral mucosa model
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DOI：
10.1002/jcp.20894
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发表时间：
2007-04-01
影响因子：
5.6
通讯作者：
Grenier, Daniel
中科院分区：
文献类型：
--
作者：
Andrian, Elisoa;Mostefaoui, Yakout;Grenier, Daniel
在生理条件下，基质金属蛋白酶（MMPs）参与牙周组织的重塑和更新，其活性受到金属蛋白酶组织抑制剂（TIMPs）的严格调控。MMPs和TIMPs之间平衡的紊乱可能导致组织过度破坏。我们先前利用一种工程化人口腔黏膜（EHOM）模型证明，牙龈卟啉单胞菌（牙周炎的主要病原体）会浸润结缔组织，并导致复层上皮从基底膜的附着显著丧失。本研究的目的是探讨牙龈卟啉单胞菌对口腔成纤维细胞和上皮细胞中MMP - 2、MMP - 9、TIMP - 1和TIMP - 2的表达及产生的影响。EHOM模型被牙龈卟啉单胞菌ATCC 33277或其衍生的无牙龈蛋白酶突变体（KDP128）感染不同时间。通过逆转录 - 聚合酶链反应（RT - PCR）分析评估MMP和TIMP的mRNA表达，同时通过酶联免疫吸附测定评估蛋白质向培养基中的分泌。牙龈卟啉单胞菌显著上调口腔上皮细胞中MMP - 2和MMP - 9的mRNA表达。这种MMP基因的激活与TIMP - 2基因的激活同时发生。然而，只有MMP - 9的mRNA表达被无牙龈蛋白酶突变体显著增强。在感染后8小时和24小时，与未感染的EHOM模型相比，牙龈卟啉单胞菌显著增加了MMP - 9的蛋白质水平。本研究报道了牙龈卟啉单胞菌调节口腔细胞产生MMP和TIMP的能力，这种现象可能导致组织破坏。
Under physiological conditions, matrix metal loproteinases (MMPs) are involved in the remodeling and turnover of periodontal tissue and their activity is tightly regulated by tissue inhibitors of metalloproteinases (TIMPs). Disturbances in the balance between MMPs and TIMPS may result in excessive tissue destruction. We previously used an engineered human oral mucosa (EHOM) model to demonstrate that Porphyromonasgingivalis, a major etiological agent of periodontitis, infiltrates connective tissue and induces significant loss of attachment of the stratified epithelium from the basement membrane. The aim of the present study was to investigate the effect of P. gingivalis on the expression and production of MMP-2, MMP-9, TIMP-1, and TIMP-2 by oral fibroblasts and epithelial cells. The EHOM model was infected with P. gingivalis ATCC 33277 or its derivative gingipain-null mutant (KDP 128) for different periods of time. MMP and TIMP mRNA expression was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) analysis, while protein secretion into the culture medium was assessed by enzyme-linked immunosorbent assays. P. gingivalis significantly up-regulated MMP-2 and MMP-9 mRNA expression by oral epithelial cells. This MMP gene activation was paralleled by TIMP-2 gene activation. However, only MMP-9 mRNA expression was significantly enhanced by the gingipain-null mutant. At 8 and 24 h post-infection, P. gingivalis increased significantly the MMP-9 protein level compared to the uninfected EHOM model. The present study reports the ability of P. gingivalis to regulate MMP and TIMP production by oral cells, a phenomenon that may contribute to tissue destruction.