Individual matrix metalloproteinases control distinct transcriptional responses in airway epithelial cells infected with Pseudomonas aeruginosa
Individual matrix metalloproteinases control distinct transcriptional responses in airway epithelial cells infected with Pseudomonas aeruginosa
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DOI：
10.1128/iai.00799-07
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发表时间：
2007-12-01
影响因子：
3.1
通讯作者：
McGuire, John K.
中科院分区：
文献类型：
--
作者：
Kassim, Sean Y.;Gharib, Sina A.;McGuire, John K.
铜绿假单胞菌感染是囊性纤维化和医院获得性肺炎的重要病原体，气道上皮是宿主-病原体相互作用的起始点。我们使用全局基因表达分析来确定依赖于基质溶素（基质金属蛋白酶7 [MMP-7]）和基质溶素-2（MMP-10）的气道上皮转录反应，这两种基质溶素由急性铜绿假单胞菌肺部感染诱导。差异基因表达提取（EDGE）分析来自野生型、Mmp 7（-/-）和Mmp 10（-/-）小鼠的铜绿假单胞菌感染的器官型气管上皮细胞培养物中的基因表达变化，确定了2，091个基质溶解素依赖性和1，628个基质溶解素-2依赖性基因的差异表达。关键节点网络分析表明，这些MMPs控制不同的基因表达程序，涉及增殖，细胞死亡，免疫反应和信号转导，以及其他宿主防御过程。我们的研究结果表明，这些基质金属蛋白酶在调节上皮细胞对假单胞菌感染的反应中发挥着独立的作用，并表明全球基因组学策略可用于评估基质金属蛋白酶的功能。
Airway epithelium is the initial point of host-pathogen interaction in Pseudomonas aeruginosa infection, an important pathogen in cystic fibrosis and nosocomial pneumonia. We used global gene expression analysis to determine airway epithelial transcriptional responses dependent on matrilysin (matrix metalloproteinase 7 [MMP-7]) and stromelysin-2 (MMP-10), two MMPs induced by acute P. aeruginosa pulmonary infection. Extraction of differential gene expression (EDGE) analysis of gene expression changes in P. aeruginosa-infected organotypic tracheal epithelial cell cultures from wild-type, Mmp7(-/-), and Mmp10(-/-) mice identified 2,091 matrilysin-dependent and 1,628 stromelysin-2-dependent genes that were differentially expressed. Key node network analysis showed that these MMPs controlled distinct gene expression programs involved in proliferation, cell death, immune responses, and signal transduction, among other host defense processes. Our results demonstrate discrete roles for these MMPs in regulating epithelial responses to Pseudomonas infection and show that a global genomics strategy can be used to assess MMP function.