Zhu Yonghua, Sun Yunjuan, Xie Lin, Jin Kunlin, Sheibani Nader, Greenberg David A
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, Calif 94945, USA.
Stroke. 2003 Oct;34(10):2483-8. doi: 10.1161/01.STR.0000088644.60368.ED. Epub 2003 Aug 28.
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.
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.
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.
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.
内皮糖蛋白（CD105）是一种膜糖蛋白，在遗传性出血性毛细血管扩张症（Osler-Rendu-Weber病）中发生突变，并且在血管生成过程中增殖的内皮细胞中表达增加。
我们在体外研究了缺氧对小鼠脑微血管内皮（bEND.3）细胞中内皮糖蛋白表达的影响以及丝裂原活化蛋白激酶（MAPK）途径的可能参与情况。
缺氧增加了bEND.3细胞中内皮糖蛋白的mRNA和蛋白表达，这与细胞外信号调节激酶（ERK）、p38 MAPK和c-Jun氨基末端激酶（JNK）的磷酸化激活有关。p38抑制剂以及激活p38的显性负性丝裂原活化蛋白激酶激酶3（MKK3）均可降低缺氧诱导的内皮糖蛋白表达。相反，组成型活性MKK3或JNK1增强了缺氧诱导的内皮糖蛋白表达。
这些结果表明，缺氧在mRNA和蛋白水平均诱导内皮糖蛋白表达，且该诱导作用受p38途径调节，可能还受JNK途径调节。
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