摘要
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。
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 alphaVbeta3, suggesting that angiostatin may play a role in embryo implantation.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2003年第5期778-783,共6页
Progress In Biochemistry and Biophysics
基金
国家重点基础研究资助项目(TG19990 5 5 90 3)
国家自然科学基金资助项目(3 0 170 3 5 7)
中国科学院知识创新工程领域前沿项目(KSCX3 IOZ 0 7)资助~~
