Variations on brain microglial gene expression of MMPs, RECK, and TIMPs in inflammatory and non-inflammatory diseases in dogs
Variations on brain microglial gene expression of MMPs, RECK, and TIMPs in inflammatory and non-inflammatory diseases in dogs
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DOI：
10.1016/j.vetimm.2011.06.029
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发表时间：
2011-11-15
影响因子：
1.8
通讯作者：
Tipold, Andrea
中科院分区：
文献类型：
--
作者：
Stein, Veronika M.;Puff, Christina;Tipold, Andrea
基质金属蛋白酶（MMP）、MMP抑制剂（TIMP，基质金属蛋白酶的组织抑制剂）和膜锚定糖蛋白RECK（具有Kazal基序的逆转诱导富含半胱氨酸的蛋白）有助于许多CNS疾病的发病机制。为了评估小胶质细胞MMP、TIMP和RECK产生在细胞外基质分解、血脑屏障（BBB）开放和随后的CNS中白细胞募集中的潜在致病作用，检查了24只患有自发发生的不同颅内和颅外（对照组）疾病的狗。通过密度梯度离心离体分离小胶质细胞，并通过定量实时聚合酶链反应（qPCR）检测其MMP-2、MMP-9、MMP-12、MMP-13、MMP-14、TIMP-1、TIMP-2和RECK的表达。对选定病例的CNS组织进行酶谱分析，以评估蛋白质水平的差异。根据组织病理学检查，将犬分为不同的疾病类别，分为有或无炎症反应的组，以及在高级诊断成像中有/无造影剂增强的组，作为BBB崩溃的函数。结果显示，与非炎症性疾病的狗相比，神经系统炎症的狗中MMP-9显著上调。MMP-9的表达增加可能导致促进白色血细胞的侵袭。此外，MMP-13的下调被发现在狗与对比增强。酶谱数据反映MMP-2 qPCR数据。总之，差异表达的基质金属蛋白酶及其抑制剂，但不是RECK，这可能是至关重要的影响一个给定的疾病的发病机制，可以证明在犬小胶质细胞。这反映了小胶质细胞库中响应CNS中的各种疾病状况的进一步途径，这一特征可能作为特定治疗的靶点特别相关。(C)2011 Elsevier B. V.保留所有权利。
Matrix metalloproteinases (MMPs), MMP inhibitors (TIMPs, tissue inhibitors of matrix metalloproteinases), and the membrane-anchored glycoprotein RECK (reversion-inducing cysteine-rich protein with Kazal motifs) contribute to the pathogenesis of many CNS diseases. To assess the potential pathogenetic roles of microglial MMP, TIMP, and RECK generation in extracellular matrix breakdown, opening of the blood brain barrier (BBB) and subsequent recruitment of leukocytes in the CNS, twenty-four dogs suffering from spontaneously occurring different intracranial and extracranial (control group) diseases were examined. Microglia cells were isolated ex vivo by density gradient centrifugation and their expressions of MMP-2, MMP-9, MMP-12, MMP-13, MMP-14, TIMP-1, TIMP-2, and RECK were examined via quantitative real-time polymerase chain reaction (qPCR). Zymography on CNS tissues in selected cases was performed to assess differences at the protein level. Dogs were grouped in different disease categories according to histopathological examinations, in groups with or without inflammatory reactions, and in groups with/without contrast enhancement in advanced diagnostic imaging as a function of BBB breakdown. The results showed a significant up-regulation of MMP-9 in dogs with inflammation in the nervous system compared to dogs with non-inflammatory diseases. An increased expression of MMP-9 might lead to a facilitated invasion of white blood cells. Furthermore, down-regulation of MMP-13 was found in dogs with contrast enhancement. Zymographical data reflected MMP-2 qPCR data. In conclusion, differential expression of MMPs and their inhibitors, but not of RECK, which might crucially influence the pathogenesis of a given disease, could be demonstrated in canine microglia. This reflects a further pathway in the microglial repertoire to respond to various disease conditions in the CNS, a characteristic that might be of particular relevance as a target for specific treatments. (C) 2011 Elsevier B.V. All rights reserved.