Expression of ADAMTS metalloproteinases in the retinal pigment epithelium derived cell line ARPE-19:: transcriptional regulation by TNFα

Expression of ADAMTS metalloproteinases in the retinal pigment epithelium derived cell line ARPE-19:: transcriptional regulation by TNFα
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DOI:
10.1016/s0167-4781(03)00047-2
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发表时间:
2003-04-15
期刊:
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子:
--
通讯作者:
McKie, N
McKie, N
中科院分区:
其他
文献类型:
--
作者:
Bevitt, DJ;Mohamed, J;McKie, N

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ADAMTS(A Disintegrin-like And Metalloprotease domain with ThromboSpondin type I motifs)是一种具有金属蛋白酶功能的多结构域蛋白,在胚胎发育、血管生成和软骨降解中具有潜在的作用。我们在这里提出的调查ADAMTS表达的眼细胞类型,ARPE-19,以期牵连他们在视网膜基质营业额。使用逆转录聚合酶链反应(RT-PCR)和北方印迹实验的组合进行表达分析,这些实验一起检测了几种ADAMTS蛋白的mRNA表达,所有这些蛋白都具有基质金属蛋白酶(MMP)的活性位点特征。其中包括ADAMTS 1、ADAMTS 2、ADAMTS 3、ADAMTS 5、ADAMTS 6、ADAMTS 7和ADAMTS 9。同时检测ADAMTS 7和ADAMTS 9的mRNA表达。在用TNF α刺激后,ARPE-19细胞中表达的ADAMTS 1、ADAMTS 6和两种ADAMTS 9转录物显示出有效的上调。ADAMTS基因在ARPE-19细胞中的表达和TNF α对某些家族成员的转录刺激可能与炎症性眼病和视网膜基质结构的损害有关,这在年龄相关性黄斑变性(ARMD)和其他视网膜病变中是明显的。(C)2003 Elsevier Science B. V.保留所有权利。
ADAMTS (A Disintegrin-like And Metalloprotease domain with ThromboSpondin type I motifs) are multidomain proteins with demonstrated metalloproteinase functionality and have potential roles in embryonic development, angiogenesis and cartilage degradation. We present here investigations of ADAMTS expression in an ocular cell type, ARPE-19, with a view to implicating them in retinal matrix turnover. Expression analysis was undertaken using a combination of reverse transcription polymerase chain reaction (RT-PCR) and Northern blotting experiments, which together detected the expression of mRNAs for several ADAMTS proteins, all of which have active site motifs characteristic of matrix metalloproteases (MMPs). These included ADAMTS1, ADAMTS2, ADAMTS3, ADAMTS5, ADAMTS6, ADAMTS7 and ADAMTS9. The expression of mRNA isoforms for ADAMTS7 and ADAMTS9 were also detected. Following stimulation with TNFalpha ADAMTS1, ADAMTS6 and both ADAMTS9 transcripts expressed in ARPE-19 cells showed a potent upregulation. The expression of ADAMTS genes in ARPE-19 cells and the transcriptional stimulation of some family members by TNFalpha may implicate them in inflammatory eye disease and the compromise of retinal matrix structure, which is evident in age-related macular degeneration (ARMD) and other retinal pathologies. (C) 2003 Elsevier Science B.V. All rights reserved.