Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus

Joon W. Shim, Johanna Sandlund, Mustafa Q. Hameed, Bonnie Blazer-Yost, Feng Zhou, Michael Klagsbrun, Joseph R. Madsen

Research output: Contribution to journalArticle

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Abstract

Heparin binding epidermal growth factor-like growth factor (HB-EGF) is an angiogenic factor mediating radial migration of the developing forebrain, while vascular endothelial growth factor (VEGF) is known to influence rostral migratory stream in rodents. Cell migratory defects have been identified in animal models of hydrocephalus; however, the relationship between HB-EGF and hydrocephalus is unclear. We show that mice overexpressing human HB-EGF with β-galactosidase reporter exhibit an elevated VEGF, localization of β-galactosidase outside the subventricular zone (SVZ), subarachnoid hemorrhage, and ventriculomegaly. In Wistar polycystic kidney rats with hydrocephalus, alteration of migratory trajectory is detected. Furthermore, VEGF infusions into the rats result in ventriculomegaly with an increase of SVZ neuroblast in rostral migratory stream, whereas VEGF ligand inhibition prevents it. Our results support the idea that excess HB-EGF leads to a significant elevation of VEGF and ventricular dilatation. These data suggest a potential pathophysiological mechanism that elevated HB-EGF can elicit VEGF induction and hydrocephalus.

Original languageEnglish (US)
Article number26794
JournalScientific Reports
Volume6
DOIs
StatePublished - May 31 2016

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Hydrocephalus
Epidermal Growth Factor
Vascular Endothelial Growth Factor A
Heparin
Intercellular Signaling Peptides and Proteins
Galactosidases
Lateral Ventricles
Polycystic Kidney Diseases
Angiogenesis Inducing Agents
Subarachnoid Hemorrhage
Prosencephalon
Dilatation
Rodentia
Animal Models
Ligands

ASJC Scopus subject areas

  • General

Cite this

Shim, J. W., Sandlund, J., Hameed, M. Q., Blazer-Yost, B., Zhou, F., Klagsbrun, M., & Madsen, J. R. (2016). Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus. Scientific Reports, 6, [26794]. https://doi.org/10.1038/srep26794

Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus. / Shim, Joon W.; Sandlund, Johanna; Hameed, Mustafa Q.; Blazer-Yost, Bonnie; Zhou, Feng; Klagsbrun, Michael; Madsen, Joseph R.

In: Scientific Reports, Vol. 6, 26794, 31.05.2016.

Research output: Contribution to journalArticle

Shim, JW, Sandlund, J, Hameed, MQ, Blazer-Yost, B, Zhou, F, Klagsbrun, M & Madsen, JR 2016, 'Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus', Scientific Reports, vol. 6, 26794. https://doi.org/10.1038/srep26794
Shim JW, Sandlund J, Hameed MQ, Blazer-Yost B, Zhou F, Klagsbrun M et al. Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus. Scientific Reports. 2016 May 31;6. 26794. https://doi.org/10.1038/srep26794
Shim, Joon W. ; Sandlund, Johanna ; Hameed, Mustafa Q. ; Blazer-Yost, Bonnie ; Zhou, Feng ; Klagsbrun, Michael ; Madsen, Joseph R. / Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus. In: Scientific Reports. 2016 ; Vol. 6.
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