Bevitt Debra J, Mohamed Jeseem, Catterall Jon B, Li Zheng, Arris Christine E, Hiscott Paul, Sheridan Carl, Langton Kevin P, Barker Michael D, Clarke Michael P, McKie Norman
Department of Rheumatology, University of Newcastle Medical School, Framlington Place, NE2 4HH, Newcastle, UK.
Biochim Biophys Acta. 2003 Apr 15;1626(1-3):83-91. doi: 10.1016/s0167-4781(03)00047-2.
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.
含血小板反应蛋白基序的解聚素样金属蛋白酶（ADAMTS）是具有已证实的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作用。我们在此展示了对一种眼细胞类型ARPE - 19中ADAMTS表达的研究，目的是探究它们在视网膜基质周转中的作用。使用逆转录聚合酶链反应（RT-PCR）和Northern印迹实验相结合的方法进行表达分析，这两种方法共同检测到了几种ADAMTS蛋白的mRNA表达，所有这些蛋白都具有基质金属蛋白酶（MMP）的活性位点基序。这些包括ADAMTS1、ADAMTS2、ADAMTS3、ADAMTS5、ADAMTS6、ADAMTS7和ADAMTS9。还检测到了ADAMTS7和ADAMTS9的mRNA异构体表达。在用肿瘤坏死因子α（TNFα）刺激后，ARPE - 19细胞中表达的ADAMTS1、ADAMTS6和两种ADAMTS9转录本均显示出显著上调。ADAMTS基因在ARPE - 19细胞中的表达以及TNFα对一些家族成员的转录刺激可能表明它们与炎症性眼病以及视网膜基质结构受损有关，这在年龄相关性黄斑变性（ARMD）和其他视网膜病变中很明显。
