Document Detail


Bone morphogenetic protein-4 enhances vascular endothelial growth factor secretion by human retinal pigment epithelial cells.
MedLine Citation:
PMID:  16514669     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Retinal pigment epithelial (RPE) cells secrete vascular endothelial growth factor (VEGF), a cytokine known to promote angiogenesis. Results from RNase protection assays (RPAs) show that RPE from non-diabetic human donors and from adult retinal pigment epithelium-19 (ARPE-19) cells expressed significant bone morphogenetic protein-4 (BMP-4) message. In addition, ARPE-19 cells cultured in high glucose (25 mM), compared to those in physiological glucose (5.5 mM) released significantly more BMP-4 into the conditioned media (CM). However, the effect of BMP-4 on the release of VEGF by ARPE-19 cells has not been studied. Accordingly, ARPE-19 cells were treated with BMP-4 to determine VEGF secretion. BMP-4 and VEGF levels in the CM and cell lysates were measured by enzyme-linked immunosorbent assay (ELISA). Cells treated with exogenous BMP-4 had higher VEGF in the CM and this treatment effect was dose- and time-dependent, while cell lysates had low levels of VEGF. Addition of cycloheximide (CHX) or actinomycin-D (ACT) significantly reduced VEGF secretion from cells treated with BMP-4, suggesting that the BMP-4-induced secretion of VEGF requires new RNA and protein synthesis. Our results suggest that BMP-4 may play a role in the regulation of ocular angiogenesis associated with diabetic retinopathy (DR) by stimulating VEGF release from RPE cells.
Authors:
Rhonda R Vogt; Richard Unda; Lee-Chuan C Yeh; Eileen K Vidro; John C Lee; Andrew T Tsin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  98     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-25     Completed Date:  2006-09-08     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1196-202     Citation Subset:  IM    
Copyright Information:
(c) 2006 Wiley-Liss, Inc.
Affiliation:
Department of Biology, The University of Texas at San Antonio, 6900 North Loop 1604 West, San Antonio, TX 78249, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Bone Morphogenetic Protein 4
Bone Morphogenetic Proteins / genetics,  metabolism*,  pharmacology,  secretion
Cell Line
Cycloheximide / pharmacology
Dactinomycin / pharmacology
Epithelial Cells / drug effects,  metabolism*,  secretion
Glucose / pharmacology
Humans
Male
Pigment Epithelium of Eye / drug effects,  metabolism*,  secretion*
Retina / drug effects,  metabolism*,  secretion*
Vascular Endothelial Growth Factor A / secretion*
Grant Support
ID/Acronym/Agency:
GM 07761/GM/NIGMS NIH HHS; GM 08194/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/BMP4 protein, human; 0/Bone Morphogenetic Protein 4; 0/Bone Morphogenetic Proteins; 0/Vascular Endothelial Growth Factor A; 50-76-0/Dactinomycin; 50-99-7/Glucose; 66-81-9/Cycloheximide

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