Document Detail

Regulation of Vascular Endothelial Growth Factor Expression by Extra Domain B Segment of Fibronectin in Endothelial Cells.
MedLine Citation:
PMID:  23150625     Owner:  NLM     Status:  Publisher    
PURPOSE: Diabetic retinopathy entails proliferation of vascular endothelial cells (ECs) and unregulated angiogenesis. We have previously shown that ECs increase the expression of an embryonic variant of fibronectin, called extra domain-B fibronectin (ED-B FN) in response to high glucose. We also showed that ED-B FN regulates EC tube morphogenesis possibly through vascular endothelial growth factor (VEGF). In the present study, we have attempted to decipher the mechanisms by which ED-B FN may modulate EC phenotype. METHODS: We hypothesize that ED-B FN regulates VEGF expression in ECs through interaction with selected integrin receptors. To test this hypothesis, we first cultured ECs in high levels of glucose to investigate for any alteration. We then used integrin-specific matrix mimetic peptides, neutralizing antibodies, and RNAi to identify the integrin(s) involved in VEGF expression. Finally, we used an animal model of diabetes to study whether these in vitro mechanisms also take place in the retina. RESULTS: Our results show the exposure of ECs to high levels of glucose increases VEGF expression. ED-B FN mediated this increase since knockdown of ED-B FN completely prevented glucose-induced VEGF expression. We then identified β1 integrin as the essential receptor involved in high glucose-induced VEGF expression. We also show that diabetes increases β1 integrin and VEGF expression in the retina, which normalizes upon ED-B knockdown. CONCLUSIONS: These findings show that high levels of glucose in diabetes increase VEGF expression in ECs through ED-B FN and β1 integrin interaction. These results provide a mechanistic basis of increased VEGF expression in diabetes.
Shali Chen; Rana Chakrabarti; Emily C Keats; Megan Chen; Subrata Chakrabarti; Zia A Khan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-13
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  -     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Pathology, University of Western Ontario, London, ON, Canada.
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