国家重点基础研究资助项目(TG1999055903)、国家自然科学基金资助项目(30170357)以及中国科学院知识创新工程领域前沿项目(KSCX3-IOZ-07)资助.
This work was supported by grants from The Special Funds for Major State Basic Research of China (TG1999055903), The National Natural Sciences Foundation of China (30170357) and The CAS Knowledge Innovation Program(KSCX3-IOZ-7).
血管生长抑素(angiostatin,AS)是一种新血管生成的抑制蛋白,它可以有效抑制内皮细胞的增殖、迁移和管状形态的产生,是肿瘤转移的有效抑制剂.肿瘤转移和胚胎植入具有惊人的相似性,AS对小鼠胚胎植入是否有作用迄今尚无报道.采用体外培养、RT-PCR和蛋白质印迹等多种方法研究了AS对小鼠胚泡中血管内皮生长因子(VEGF)及其受体KDR、基质金属蛋白酶(MMPs)及其组织抑制剂(TIMPs)的影响.研究显示,AS下调了VEGF及其受体KDR、MMP-2和MMP-9的表达,而上调了TIMP-1和TIMP-2的表达.应用整合素αVβ3的特异性抑制剂Echistatin与AS共同处理胚泡,结果显示,Echistatin减弱了AS对MMP-2的下调作用及对TIMP-2的上调作用.以上结果提示:AS可能通过与整合素αVβ3相互作用调节胚泡中VEGF、MMPs和TIMPs的表达,从而影响胚泡的植入过程.
Angiostatin, a 38 ku fragment encompassing the four kringle region of plasminogen, has been identified and characterized to be a potent inhibitor of neovascularization and tumor metastasis. There is a strikingly similarity between tumor metastasis and embryo implantation. However, effect of angiostatin in the mouse blastocyst has never been reported. The results showed for the first time that angiostatin down-regulated the expression of matrix metalloproteinase-2(MMP-2), MMP-9, vascular endothelial growth factor family and its receptor, KDR, and up-regulated the expression of tissue inhibitor of metalloproteinase-1(TIMP-1) and TIMP-2 expression by binding with integrin αVβ3, suggesting that angiostatin may play a role in embryo implantation.
赵田夫,张键,李晶,曹宇静,李素敏,周家喜,李福洋,药立波,段恩奎.血管生长抑素在小鼠胚泡中的调节作用[J].生物化学与生物物理进展,2003,30(5):778-783
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