Vascular endothelial growth factor induces heparin-binding epidermal growth factor-like growth factor in vascular endothelial cells

Burak M. Arkonac, Lauren C. Foster, Nicholas E.S. Sibinga, Cam Patterson, Kaihua Lai, Jer Chia Tsai, Mu En Lee, Mark A. Perrella, Edgar Haber

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Although several cytokines and growth factors have been shown to regulate vascular endothelial growth factor (VEGF) production, little is known about how VEGF may regulate growth factors that have known mitogenic and chemotactic actions on mesenchymal cells (which are involved in the maturation of the angiogenic process). We investigated the effect of VEGF on heparin-binding epidermal growth factor-like growth factor (HB-EGF) expression in human umbilical vein endothelial cells. HB-EGF mRNA was induced by 8-fold after 2 h of VEGF stimulation, and it returned to base line within 6 h. VEGF did not alter the half-life of HB-EGF mRNA (55 min). Nuclear run- on experiments showed a 4.9-fold increase in HB-EGF gene transcription within 2 h of VEGF stimulation, and Western analysis demonstrated an associated increase in cellular HB-EGF protein. We found that platelet-derived growth factor-BB (PDGF-BB) mRNA was also induced 3-fold after 5 h of VEGF stimulation, whereas neither endothelin 1 nor transforming growth factor-β1 was regulated by VEGF. Finally, conditioned medium from VEGF-stimulated endothelial cells produced an increase in DNA synthesis in vascular smooth muscle cells, and this effect was blocked by a neutralizing antibody to PDGF. The induction of HB-EGF and PDGF-BB expression in endothelial cells may represent the mechanism by which VEGF recruits mesenchymal cells to form the medial and adventitial layers of arterioles and venules during the course of angiogenesis.

Original languageEnglish (US)
Pages (from-to)4400-4405
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number8
DOIs
StatePublished - Feb 20 1998
Externally publishedYes

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Endothelial cells
Epidermal Growth Factor
Vascular Endothelial Growth Factor A
Heparin
Intercellular Signaling Peptides and Proteins
Endothelial Cells
Messenger RNA
Adventitia
Venules
Human Umbilical Vein Endothelial Cells
Arterioles
Transforming Growth Factors
Endothelin-1
Transcription
Conditioned Culture Medium
Neutralizing Antibodies
Vascular Smooth Muscle
Smooth Muscle Myocytes
Half-Life
Muscle

ASJC Scopus subject areas

  • Biochemistry

Cite this

Vascular endothelial growth factor induces heparin-binding epidermal growth factor-like growth factor in vascular endothelial cells. / Arkonac, Burak M.; Foster, Lauren C.; Sibinga, Nicholas E.S.; Patterson, Cam; Lai, Kaihua; Tsai, Jer Chia; Lee, Mu En; Perrella, Mark A.; Haber, Edgar.

In: Journal of Biological Chemistry, Vol. 273, No. 8, 20.02.1998, p. 4400-4405.

Research output: Contribution to journalArticle

Arkonac, Burak M. ; Foster, Lauren C. ; Sibinga, Nicholas E.S. ; Patterson, Cam ; Lai, Kaihua ; Tsai, Jer Chia ; Lee, Mu En ; Perrella, Mark A. ; Haber, Edgar. / Vascular endothelial growth factor induces heparin-binding epidermal growth factor-like growth factor in vascular endothelial cells. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 8. pp. 4400-4405.
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