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

Yonghua Zhu, Yunjuan Sun, Lin Xie, Kunlin Jin, Nader Sheibani, David A. Greenberg

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2483-2488
Number of pages6
JournalStroke
Volume34
Issue number10
DOIs
StatePublished - 1 Oct 2003

Fingerprint

Mitogen-Activated Protein Kinases
Endothelial Cells
Brain
Hereditary Hemorrhagic Telangiectasia
Phosphotransferases
MAP Kinase Kinase 3
MAP Kinase Kinase 4
Messenger RNA
Mitogen-Activated Protein Kinase Kinases
Membrane Glycoproteins
p38 Mitogen-Activated Protein Kinases
Endoglin
Hypoxia
Proteins

Keywords

  • Angiogenesis
  • Brain
  • Endoglin
  • Endothelium
  • Hypoxia
  • Mitogen-activated protein kinases
  • Protein kinases

Cite this

Zhu, Yonghua ; Sun, Yunjuan ; Xie, Lin ; Jin, Kunlin ; Sheibani, Nader ; Greenberg, David A. / Hypoxic induction of endoglin via mitogen-activated protein kinases in mouse brain microvascular endothelial cells. In: Stroke. 2003 ; Vol. 34, No. 10. pp. 2483-2488.
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Hypoxic induction of endoglin via mitogen-activated protein kinases in mouse brain microvascular endothelial cells. / Zhu, Yonghua; Sun, Yunjuan; Xie, Lin; Jin, Kunlin; Sheibani, Nader; Greenberg, David A.

In: Stroke, Vol. 34, No. 10, 01.10.2003, p. 2483-2488.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hypoxic induction of endoglin via mitogen-activated protein kinases in mouse brain microvascular endothelial cells

AU - Zhu, Yonghua

AU - Sun, Yunjuan

AU - Xie, Lin

AU - Jin, Kunlin

AU - Sheibani, Nader

AU - Greenberg, David A.

PY - 2003/10/1

Y1 - 2003/10/1

N2 - 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.

AB - 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.

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