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Circulation. 2002;106:2263-2270
Published online before print September 30, 2002, doi: 10.1161/01.CIR.0000033830.36431.46
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(Circulation. 2002;106:2263.)
© 2002 American Heart Association, Inc.


Basic Science Reports

Stimulation of Id1 Expression by Bone Morphogenetic Protein Is Sufficient and Necessary for Bone Morphogenetic Protein–Induced Activation of Endothelial Cells

Gudrun Valdimarsdottir, MS; Marie-José Goumans, PhD; Alexander Rosendahl, PhD; Martijn Brugman, MS; Susumu Itoh, PhD; Franck Lebrin, PhD; Paschalis Sideras, PhD; Peter ten Dijke, PhD

From the Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam, the Netherlands (G.V., M.-J.G., M.B., S.I., F.L. P.t.D.), and the Department of Immunology, Biomedical Center Lund University, Lund, Sweden (A.R., P.S.).

Correspondence to Peter ten Dijke, Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. E-mail p.t.dijke{at}nki.nl

Background— Bone morphogenetic proteins (BMPs) are multifunctional proteins that regulate the proliferation, differentiation, and migration of a large variety of cell types. Like other members of the transforming growth factor-ß family, BMPs elicit their cellular effects through activating specific combinations of type I and type II serine/threonine kinase receptors and their downstream effector proteins, which are termed Smads. In the present study, we investigated BMP receptor/Smad expression and signaling in endothelial cells (ECs) and examined the effects of BMP on EC behavior.

Methods and Results— Immunohistochemical analysis of tissue sections of human colon and mouse heart and aorta showed that BMP receptors are expressed in ECs in vivo. Bovine aortic ECs and mouse embryonic ECs were found to express BMP receptors and their Smads. BMP receptor activation induced the phosphorylation of specific Smad proteins and promoted EC migration and tube formation. Id1 was identified as a BMP/Smad target in ECs. Ectopic expression of Id1 mimicked BMP-induced effects. Importantly, specific interference with Id1 expression blocked BMP-induced EC migration.

Conclusions— The BMP/Smad pathway can potently activate the endothelium. Id1 expression is strongly induced by BMP in ECs. Ectopic expression of Id1 induces EC migration and tube formation. Moreover, Id1 played a critical role in mediating BMP-induced EC migration.


Key Words: angiogenesis • signal transduction • growth substances




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