Hypoxic induction of endoglin via mitogen-activated protein kinases in mouse brain microvascular endothelial cells
Hypoxic induction of endoglin via mitogen-activated protein kinases in mouse brain microvascular endothelial cells
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DOI：
10.1161/01.str.0000088644.60368.ed
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发表时间：
2003-10-01
期刊：
影响因子：
8.3
通讯作者：
Greenberg, DA
中科院分区：
文献类型：
--
作者：
Zhu, YH;Sun, YJ;Greenberg, DA
背景与目的：Endoglin(CD105)是一种在遗传性出血性毛细血管扩张症(Osler-rendu-Weber病)中发生突变的膜糖蛋白，在血管生成过程中，其在增殖的内皮细胞中的表达增加。方法：体外研究低氧对小鼠脑微血管内皮细胞(bEND.3)中endoglin表达的影响及丝裂原活化蛋白激酶(MAPK)的可能参与。结果缺氧使bEND.3细胞中endoglin的mRNA和蛋白表达增加，这与细胞外信号相关蛋白(ERK)、p38MAPK和Jun氨基端(JNK)的磷酸化有关。P38的抑制剂减少了低氧诱导的endoglin表达，显性负MAPK激酶3(MKK3)也是如此，后者激活了p38。相反，MKK3或JNK1的结构活性增强了低氧诱导的Endoglin的表达。结论--这些结果表明低氧诱导Enoglin在mRNA和蛋白水平上的表达，其诱导受p38和JNK信号通路的调节。
Background and Purpose-Endoglin (CD105) is a membrane glycoprotein that is mutated in hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber disease) and shows increased expression in proliferating endothelial cells during angiogenesis.Methods-We investigated the effect of hypoxia on endoglin expression in murine cerebral microvascular endothelial (bEND.3) cells in vitro and the possible involvement of mitogen-activated protein kinase (MAPK) pathways.Results-Hypoxia increased endoglin mRNA and protein expression in bEND.3 cells, which was associated with phosphoactivation of extracellular signal-related kinase (ERK), p38 MAPK, and Jun amino-terminal kinase (JNK). Inhibitors of p38 decreased hypoxic induction of endoglin expression, as did dominant negative MAPK kinase 3 (MKK3), which activates p38. In contrast, constitutively active MKK3 or JNK1 potentiated the hypoxic induction of endoglin.Conclusions-These results indicate that hypoxia induces the expression of endoglin at both the mRNA and protein levels and that induction is regulated by the p38 and perhaps also JNK pathways.