Hypoxic induction of endoglin via mitogen-activated protein kinases in mouse brain microvascular endothelial cells.

Publications // Sheibani Lab // Oct 01 2003

PubMed ID: 12947156

Author(s): Zhu Y, Sun Y, Xie L, Jin K, Sheibani N, Greenberg DA. Hypoxic induction of endoglin via mitogen-activated protein kinases in mouse brain microvascular endothelial cells. Stroke. 2003 Oct;34(10):2483-8. Epub 2003 Aug 28. PMID 12947156

Journal: Stroke, Volume 34, Issue 10, Oct 2003

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.