Transcript profile of cellular senescence-related genes in Fuchs endothelial corneal dystrophy.
Transcript profile of cellular senescence-related genes in Fuchs endothelial corneal dystrophy.
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DOI：
10.1016/j.exer.2014.10.011
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发表时间：
2014-12
影响因子：
3.4
通讯作者：
Jun, Albert S.
中科院分区：
文献类型：
--
作者：
Matthaei, Mario;Zhu, Angela Y.;Kallay, Laura;Eberhart, Charles G.;Cursiefen, Claus;Jun, Albert S.
关键词：
Fuchs内皮性角膜营养不良(FECD)是一种遗传异质性疾病。假设细胞衰老可能与FECD的发病机制有关，对遗传未分化的迟发性FECD内皮样本进行了分析，以确定特定衰老相关转录本的共同变化。从临床诊断为终末期FECD的板层角膜移植患者的21例FECD内皮细胞和正常尸检的12例内皮细胞标本中提取总RNA。用TaqMan低密度阵列(TLDA)卡片分析89个细胞衰老相关转录本的差异表达。结果验证使用个别实时聚合酶链式反应分析。TLDA分析显示31个转录本(折叠式变化和Gt；1.5；p<；0.05)存在差异表达。其中27例显著上调，4例显著下调。在所有可评估的FECD样本中，结构性活性和活性氧产生酶NOX4的mRNA水平都显著升高。此外，在FECD组织中，CDKN2A及其转录激活因子ETS1和ARHGAP18(Senex)的表达增加，CDKN2A抑制物ID1的表达降低。NOX4在FECD内皮细胞中持续过表达，提示其作为致病因子和潜在的新的治疗靶点在FECD中的作用。CDKN2A途径的转录上调为FECD内皮细胞衰老的增加提供了进一步的证据。
Fuchs endothelial corneal dystrophy (FECD) is a genetically heterogeneous disease. Hypothesizing that cellular senescence may be relevant in FECD pathogenesis, genetically undifferentiated late-onset FECD endothelial samples were analyzed to identify common changes of specific senescence-related transcripts. Total RNA was extracted from 21 FECD endothelial samples retrieved from patients undergoing lamellar keratoplasty due to clinically diagnosed end-stage FECD and from 12 endothelial samples retrieved from normal autopsy eyes. Taqman low density array (TLDA) cards were used to analyze differential expression of 89 cellular senescence-related transcripts. Result validation was performed using individual real-time PCR assays. TLDA-analysis demonstrated differential expression of 31 transcripts (fold-change >1.5; p<0.05). Thereof, 27 showed significant up-regulation and 4 significant down-regulation. Markedly elevated mRNA-levels of the constitutively active and reactive oxygen species-generating enzyme NOX4 were found in all evaluable FECD samples. In addition, increased expression of CDKN2A and its transcriptional activators ETS1 and ARHGAP18 (SENEX) along with decreased expression of CDKN2A inhibitor ID1 were detected in FECD samples. Consistent over-expression of NOX4 in FECD endothelial samples suggests a role as pathogenic factor and as a potential new treatment target in FECD. Transcriptional up-regulation of the CDKN2A-pathway provides further evidence for increased cellular senescence in FECD endothelium.
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影响因子：
2.8
作者：
Matthaei M;Lackner EM;Meng H;Hicks JL;Meeker AK;Eberhart CG;Jun AS
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作者：
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