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LDB2 regulates the expression of DLL4 through the formation of oligomeric complexes in endothelial cells

Authors
 Hyun-Jung Choi  ;  Seung-Sik Rho  ;  Dong-Hoon Choi  ;  Young-Guen Kwon 
Citation
 BMB Reports, Vol.51(1) : 21-26, 2018 
Journal Title
 BMB Reports 
ISSN
 1976-6696 
Issue Date
2018
MeSH
Animals ; Animals, Genetically Modified ; Endothelial Cells/metabolism* ; Gene Knockdown Techniques ; Human Umbilical Vein Endothelial Cells ; Humans ; Intercellular Signaling Peptides and Proteins/biosynthesis* ; Intercellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/biosynthesis* ; Intracellular Signaling Peptides and Proteins/genetics ; LIM Domain Proteins/deficiency ; LIM Domain Proteins/genetics ; LIM Domain Proteins/metabolism* ; Neovascularization, Physiologic ; Promoter Regions, Genetic ; RNA, Small Interfering/genetics ; Signal Transduction ; Transcription Factors/deficiency ; Transcription Factors/genetics ; Transcription Factors/metabolism* ; Transcription, Genetic ; Vascular Endothelial Growth Factor A/metabolism ; Zebrafish ; Zebrafish Proteins/biosynthesis* ; Zebrafish Proteins/deficiency ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism*
Keywords
Angiogenesis ; DLL4 ; Endothelial cells ; LDB2 ; LMO2/TAL1/GATA2 complex ; Sprouting
Abstract
Delta-like ligand 4 (DLL4) expression in endothelial cells is intimately associated with angiogenic sprouting and vascular remodeling, but the precise mechanism of transcriptional regulation of DLL4 remains incompletely understood. Here, we showed that LIM-domain binding protein 2 (LDB2) plays an important role in regulating basal DLL4 and VEGF-induced DLL4 expression. Knockdown of LDB2 using siRNA enhanced endothelial sprouting and tubular network formation in vitro. Injection of ldb2-morpholino resulted in defective development of intersegmental vessels in zebrafish. Reduction or overexpression of LDB2 in endothelial cells decreased or increased DLL4 expression. LDB2 regulated DLL4 promoter activity by binding to its promoter region and the same promoter region was occupied and regulated by the LMO2/TAL1/GATA2 complex. Interestingly, LDB2 also mediated VEGF-induced DLL4 expression in endothelial cells. The regulation of DLL4 by the LDB2 complex provides a novel mechanism of DLL4 transcriptional control that may be exploited to develop therapeutics for aberrant vascular remodeling.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/163421
Files in This Item:
T201800242.pdf Download
DOI
10.5483/BMBRep.2018.51.1.140
Appears in Collections:
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단)
Yonsei Authors
최현정(Choi, Hyun-Jung) ORCID logo https://orcid.org/0000-0003-3695-3420
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