Canine uterine bacterial infection induces upregulation of proteolysis-related genes and downregulation of homeobox and zinc finger factors.
Canine uterine bacterial infection induces upregulation of proteolysis-related genes and downregulation of homeobox and zinc finger factors.
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DOI：
10.1371/journal.pone.0008039
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发表时间：
2009-11-26
期刊：
影响因子：
3.7
通讯作者：
Pejler G
中科院分区：
文献类型：
--
作者：
Hagman R;Rönnberg E;Pejler G
细菌感染与脓毒症的严重并发症是一种常见和严重的疾病，是世界范围内死亡的主要原因。因此，为了应对过多的细菌感染，迫切需要确定宿主反应过程中的分子机制，以便确定潜在的治疗干预靶点和疾病的生物标记物。在这里，我们通过研究自然发生的子宫细菌感染的母犬子宫中的全局基因表达来解决这个问题。分析表明，在患病动物的子宫中，几乎有800个基因显著上调(P<；0.05)(2倍)。其中包括大量的趋化因子和细胞因子基因，以及与炎症细胞外渗、抗菌作用、补体系统和先天免疫反应相关的基因，以及与蛋白多糖相关的基因。与蛋白质分解相关的基因也有惊人的表现。与抗原呈递有关的免疫球蛋白成分和基因也明显上调，这表明了一种强大的适应性免疫反应。细菌感染还与近700个基因的显著下调有关，其中各种同源盒和锌指转录因子高度表达。总而言之，这些发现勾勒出了与子宫细菌感染有关的分子模式。这项研究发现了许多以前与细菌疾病无关的基因表达的变化，其中几个基因可能被评估为潜在的疾病生物标记物或治疗靶点。重要的是，由于人类和狗表现出遗传相似性，并发展出具有许多共同特征的疾病，因此这里确定的分子事件很可能反映出患有类似疾病的人类的相应情况。
Bacterial infection with the severe complication of sepsis is a frequent and serious condition, being a major cause of death worldwide. To cope with the plethora of occurring bacterial infections there is therefore an urgent need to identify molecular mechanisms operating during the host response, in order both to identify potential targets for therapeutic intervention and to identify biomarkers for disease. Here we addressed this issue by studying global gene expression in uteri from female dogs suffering from spontaneously occurring uterine bacterial infection. The analysis showed that almost 800 genes were significantly (p<0.05) upregulated (>2-fold) in the uteri of diseased animals. Among these were numerous chemokine and cytokine genes, as well as genes associated with inflammatory cell extravasation, anti-bacterial action, the complement system and innate immune responses, as well as proteoglycan-associated genes. There was also a striking representation of genes associated with proteolysis. Robust upregulation of immunoglobulin components and genes involved in antigen presentation was also evident, indicating elaboration of a strong adaptive immune response. The bacterial infection was also associated with a significant downregulation of almost 700 genes, of which various homeobox and zinc finger transcription factors were highly represented. Together, these finding outline the molecular patterns involved in bacterial infection of the uterus. The study identified altered expression of numerous genes not previously implicated in bacterial disease, and several of these may be evaluated for potential as biomarkers of disease or as therapeutic targets. Importantly, since humans and dogs show genetic similarity and develop diseases that share many characteristics, the molecular events identified here are likely to reflect the corresponding situation in humans afflicted by similar disease.
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Fe65结合茶会，抑制灵长类动物特异性caspase-4的表达。
影响因子：
3.7
作者：
Kajiwara Y;Akram A;Katsel P;Haroutunian V;Schmeidler J;Beecham G;Haines JL;Pericak-Vance MA;Buxbaum JD
通讯作者：
Buxbaum JD
DOI：
10.1073/pnas.2133048100
发表时间：
2003-10-14
影响因子：
11.1
作者：
Hong, JW;Allen, CE;Wu, LC
通讯作者：
Wu, LC
影响因子：
2.8
作者：
Hagman, R.;Kindahl, H.;Lagerstedt, A. -S.
通讯作者：
Lagerstedt, A. -S.
影响因子：
10.6
作者：
Edwards DR;Handsley MM;Pennington CJ
通讯作者：
Pennington CJ
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP