IOVS AJP: Gastrointestinal and Liver Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

P<P, published online ahead of print April 30, 2008
(Investigative Ophthalmology and Visual Science. )
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.08-1760
This Article
Right arrow Full Text (P<P[PDF])
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Maiti, D.
Right arrow Articles by Duh, E. J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maiti, D.
Right arrow Articles by Duh, E. J.

Article

Vascular endothelial growth factor induces MEF2C and MEF2-dependent activity in endothelial cells

Debasish Maiti 1, Zhenhua Xu 1, and Elia J. Duh 1*

1 Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

* To whom correspondence should be addressed. E-mail: eduh{at}jhmi.edu.


  Abstract

PURPOSE. Vascular endothelial growth factor is a key regulator of physiological and pathological angiogenesis, including proliferative diabetic retinopathy. Although much is known about the major upstream signaling pathways of VEGF in endothelial cells, less is known about key transcription factors involved in VEGF action. The transcription factor myocyte enhancer factor 2C (MEF2C) is thought to play an important role in vasculogenesis and angiogenesis during vascular development. The purpose of this study was to investigate the regulation of MEF2C expression and MEF2-dependent activity in endothelial cells by VEGF. METHODS. Expression of MEF2C in human retinal endothelial cells (HRECs) and HUVECs was assayed by real-time PCR and western blot. VEGF regulation of MEF2-dependent transcription was studied using a MEF2-luciferase reporter construct, containing three copies of a high affinity MEF2 binding site. The effect of MEF2 on endothelial cell migration was evaluated using a dominant-negative MEF2C mutant. RESULTS. VEGF induced MEF2C expression in a dose- and time-dependent fashion. This induction was completely abrogated by inhibition of protein kinase C and partially blocked by inhibition of PKC-{beta} and PKC-{delta}. In addition to regulating MEF2C expression, VEGF stimulated transcription from a MEF2-dependent promoter. VEGF stimulation of transcription was significantly reduced by inhibition of calcineurin, CaMKII, p38 MAPK, and PKC, but not by inhibition of ERK1/2 or BMK1/ERK5. Transfection of a dominant-negative mutant of MEF2C significantly inhibited VEGF-stimulated endothelial cell migration. CONCLUSIONS. These results implicate VEGF as a key regulator of MEF2C, and suggest that MEF2 may be important in mediator of VEGF in endothelial cells.

Key Words: diabetic retinopathy, angiogenesis, growth factors






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2008 by the Association for Research in Vision and Ophthalmology