Gene Expression Dynamics during Diabetic Periodontitis
Gene Expression Dynamics during Diabetic Periodontitis
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DOI：
10.1177/0022034512465292
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发表时间：
2012-12-01
影响因子：
7.6
通讯作者：
Graves, D. T.
中科院分区：
文献类型：
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作者：
Andriankaja, O. M.;Galicia, J.;Graves, D. T.
糖尿病损害牙周炎症的消退。我们通过使用结扎器诱导2型糖尿病大鼠牙周炎，探索了糖尿病牙周组织炎症改变的途径。7d后摘除结扎，4d后给予肿瘤坏死因子抑制剂(Pegsunercept)或赋形剂单独处理，安乐死。从牙周组织中提取RNA，用信使核糖核酸图谱进行检测，并进一步按功能标准进行分析。我们发现1,754个基因显著上调，1,243个基因下调(p<；0.05)。功能分析显示，神经元相关和视网膜相关基因簇以及与细胞活动和信号相关的基因簇上调。其他基因则被肿瘤坏死因子抑制下调，包括与宿主防御、细胞凋亡、细胞信号和活性以及凝血/止血/补体相关的基因。对于选定的基因，微阵列和RT-PCR的结果是一致的。免疫组织化学进一步研究了PPAR-α的抗炎作用，发现PPAR-α在牙周炎症消退过程中牙周组织中表达上调，并被糖尿病抑制。结果表明，糖尿病增强型炎症同时上调和下调与细胞活动和细胞信号有关的基因，其中主要上调与宿主反应、细胞凋亡和凝血/内稳态/补体相关的基因，下调神经元、视网膜和能量/代谢相关基因的mRNA水平。
Diabetes impairs the resolution of periodontal inflammation. We explored pathways altered by inflammation in the diabetic periodontium by using ligatures to induce periodontitis in type-2 diabetic Goto-Kakizaki rats. Ligatures were removed after 7 days, and rats were then treated with TNF inhibitor (pegsunercept) or vehicle alone and euthanized 4 days later. RNA was extracted from periodontal tissue, examined by mRNA profiling, and further analyzed by functional criteria. We found that 1,754 genes were significantly up-regulated and 1,243 were down-regulated by pegsunercept (p < 0.05). Functional analysis revealed up-regulation of neuron-associated and retina-associated gene clusters as well as those related to cell activity and signaling. Others were down-regulated by TNF inhibition and included genes associated with host defense, apoptosis, cell signaling and activity, and coagulation/hemostasis/complement. For selected genes, findings with microarray and rt-PCR agreed. PPAR-alpha was investigated further by immunohistochemistry due to its anti-inflammatory function and was found to be up-regulated in the gingiva during the resolution of periodontal inflammation and suppressed by diabetes. The results indicate that diabetes-enhanced inflammation both up- and down-regulates genes involved in cellular activity and cell signaling, while it predominantly up-regulates genes involved in the host response, apoptosis, and coagulation/homeostasis/complement and down-regulates mRNA levels of neuron, retina, and energy/metabolism-associated genes.