BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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LDB2 regulates the expression of DLL4 through the formation of oligomeric complexes in endothelial cells

  • Choi, Hyun-Jung (Severance Integrative Research Institute for Cerebral & Cardiovascular Diseases (SIRIC), College of Medicine, Yonsei University) ;
  • Rho, Seung-Sik (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Choi, Dong-Hoon (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Kwon, Young-Guen (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University)
  • 투고 : 2017.07.21
  • 심사 : 2017.09.14
  • 발행 : 2018.01.31
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초록

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 over-expression 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.

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참고문헌

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