Hypoxic induction of endoglin via mitogen-activated protein kinases in mouse brain microvascular endothelial cells.
OBJECTIVE
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.
Zhu
Yonghua
Y
Buck Institute for Age Research, 8001 Redwood Blvd, Novato, Calif 94945, USA.
Sun
Yunjuan
Y
Xie
Lin
L
Jin
Kunlin
K
Sheibani
Nader
N
Greenberg
David A
DA
D000818:Animals; D015703:Antigens, CD; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D004195:Disease Models, Animal; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005799:Genes, Dominant; D006801:Humans; D048371:MAP Kinase Kinase 3; D008297:Male; D051379:Mice; D008833:Microcirculation / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1; D011505:Protein-Tyrosine Kinases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048371:MAP Kinase Kinase 3; C482530:MAP2K3 protein, human; C482531:Map2k3 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases