| Regulation of Cyr61/CCN1 expression by hypoxia through cooperation of c-Jun/AP-1 and HIF-1α in retinal vascular endothelial cells. | |
| | |
MedLine Citation:
|
PMID: 21029732 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Hypoxia is the most important factor in the pathogenesis of diabetic retinopathy. Cysteine-rich 61 (Cyr61) is one of the angiogenic factors involved in the development of proliferative diabetic retinopathy (PDR). The aim of this study was to investigate the mechanism of hypoxia-induced Cyr61 expression in retinal vascular endothelial cells. The hypoxia-induced expression of mRNA and protein of Cyr61 was studied in monkey choroidal retinal vascular endothelial (RF/6A) cells. Luciferase reporter assays and electrophoretic mobility shift assays were used to identify the hypoxia responsible region and transcription factors in the Cyr61 promoter. Chromatin immunoprecipitation and immunoprecipitation were performed to study the role of hypoxia-inducible factor (HIF)-1α and c-Jun/activator protein-1 (AP-1) in Cyr61 transcriptional regulation. The results showed that hypoxia significantly induced Cyr61 mRNA and protein expression in RF/6A cells. The effect was mediated through phosphorylation of c-Jun. Luciferase assays, electrophoretic mobility shift assays, chromatin immunoprecipitation and immunoprecipitation showed that HIF-1α interacted with c-Jun/AP-1 and their binding on the AP-1 binding motif within the Cyr61 promoter induced the expression of Cyr61. In conclusion, hypoxia controlled the transcriptional regulation of the Cyr61 gene in RF/6A cells by cooperation of HIF-1α and c-Jun/AP-1. Cyr61 might play an important role in ischemic retinal diseases, such as PDR. |
| | |
Authors:
|
Jian-Jang You; Chung-May Yang; Muh-Shy Chen; Chang-Hao Yang |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-26 |
Journal Detail:
|
Title: Experimental eye research Volume: 91 ISSN: 1096-0007 ISO Abbreviation: Exp. Eye Res. Publication Date: 2010 Dec |
Date Detail:
|
Created Date: 2010-11-29 Completed Date: 2010-12-30 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0370707 Medline TA: Exp Eye Res Country: England |
Other Details:
|
Languages: eng Pagination: 825-36 Citation Subset: IM |
Copyright Information:
|
Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
|
Keelung General Hospital, Department of Health, The Executive Yuan, Keelung, Taiwan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Anoxia / metabolism* Blotting, Western Cells, Cultured Cysteine-Rich Protein 61 / genetics*, metabolism Electrophoretic Mobility Shift Assay Endothelium, Vascular / cytology, metabolism* Enzyme-Linked Immunosorbent Assay Gene Expression Regulation / physiology* Genes, Reporter Hypoxia-Inducible Factor 1, alpha Subunit / metabolism* Macaca Mutagenesis, Site-Directed Neovascularization, Physiologic Phosphorylation Proto-Oncogene Proteins c-jun / metabolism* RNA, Messenger / genetics Retinal Vessels / cytology Reverse Transcriptase Polymerase Chain Reaction Transcription Factor AP-1 / metabolism* |
| Chemical | |
Reg. No./Substance:
|
0/Cysteine-Rich Protein 61; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; 0/Transcription Factor AP-1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A novel function for KIF13B in germ cell migration.
Next Document: Differential roles of AMPK?1 and AMPK?2 in regulating 4-HNE-induced RPE cell death and permeability.