Hirohata Satoshi, Inagaki Junko, Ohtsuki Takashi
Department of Medical Technology, Graduate School of Health Sciences, Okayama University.
Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.
Yakugaku Zasshi. 2017;137(7):811-814. doi: 10.1248/yakushi.16-00236-4.
A disintegrin and metalloproteinase with thrombospondin motif-1 (ADAMTS1) was initially cloned from a colon cachexia cell line. In the last 20 years, novel matrix metalloproteinase (MMP) genes were found, and in addition to their original members (MMPs and membrane-type MMPs), the current MMP family contains a disintegrin and metalloproteinases (ADAMs) and ADAMTS. ADAM and ADAMTS play essential roles in organogenesis as well as various diseases including osteoarthritis. ADAMTS has 19 members and can be divided into several groups according to their substrates. ADAMTS1, the first member of ADAMTS identified, is located on chromosome 21 very close to another ADAMTS member, ADAMTS5. Interestingly, ADAMTS1 is not highly expressed in normal tissues. One stimulation such as inflammation quickly induces ADAMTS1 expression. We found that hypoxia induced ADAMTS1 expression in endothelial cells, and serum ADAMTS1 levels were elevated in acute myocardial infarction patients. Once the artery was reperfused, the serum ADAMTS1 level quickly returned to the normal level. We also found that ADAMTS1 has specific roles in angiogenesis and lymphangiogenesis, and these functions were not related to its protease activity. It is also interesting that ADAMTS1 is likely to have a unique role in the tumor microenvironment. We also analyzed ADAMTS1-deficient mice and the results suggested that ADAMTS1 has diverse biological functions.
含血小板反应蛋白基序的解聚素和金属蛋白酶-1（ADAMTS1）最初是从结肠恶病质细胞系中克隆出来的。在过去20年里，发现了新的基质金属蛋白酶（MMP）基因，除了其原始成员（MMPs和膜型MMPs）外，目前的MMP家族还包括解聚素和金属蛋白酶（ADAMs）以及ADAMTS。ADAM和ADAMTS在器官发生以及包括骨关节炎在内的各种疾病中发挥着重要作用。ADAMTS有19个成员，可根据其底物分为几组。ADAMTS1是最早被鉴定出的ADAMTS成员，位于21号染色体上，与另一个ADAMTS成员ADAMTS5非常接近。有趣的是，ADAMTS1在正常组织中表达不高。诸如炎症等刺激可迅速诱导ADAMTS1表达。我们发现缺氧可诱导内皮细胞中ADAMTS1表达，急性心肌梗死患者血清ADAMTS1水平升高。一旦动脉再灌注，血清ADAMTS1水平迅速恢复到正常水平。我们还发现ADAMTS1在血管生成和淋巴管生成中具有特定作用，且这些功能与其蛋白酶活性无关。同样有趣的是，ADAMTS1可能在肿瘤微环境中具有独特作用。我们还分析了ADAMTS1基因敲除小鼠，结果表明ADAMTS1具有多种生物学功能。
