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(Stroke. 2003;34:2483.)
© 2003 American Heart Association, Inc.

Original Contributions

Hypoxic Induction of Endoglin via Mitogen-Activated Protein Kinases in Mouse Brain Microvascular Endothelial Cells

Yonghua Zhu, MD; Yunjuan Sun, MD; Lin Xie, BS; Kunlin Jin, MD, PhD; Nader Sheibani, PhD David A. Greenberg, MD, PhD

From the Buck Institute for Age Research, Novato, Calif (Y.Z., Y.S., L.X., K.J., D.A.G.), and Department of Pharmacology and Ophthalmology and Visual Sciences, University of Wisconsin, Madison (N.S.).

Correspondence to David A. Greenberg, MD, PhD, Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945. E-mail dgreenberg{at}buckinstitute.org

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.

Key Words: angiogenesis • brain • endoglin • endothelium • hypoxia • mitogen-activated protein kinases • protein kinases

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