Protective effects of transcription factor HESR1 on retinal vasculature.
HESR1 is a basic helix-loop-helix transcription factors regulated by the Notch signaling pathway in vertebrate and Drosophila embryos, and is related to the HES/Hairy/E (sp1) family. HESR1 is a downstream target of Notch in endothelial cells and could be an effector of Notch signaling in these cells. HESR1 is necessary for the induction of a tubular network and for continued maintenance of mature and quiescent blood vessels. To examine the role of HESR1 in retinal neovascularization, we transfected retinal vascular endothelial cells (HRCECs) with the HESR1 gene and studied its effects on the expression of angiogenic factors, on the proliferation and migration of endothelial cells, and on the formation of tube-like structures (TLSs). Overexpression of HESR1 downregulated VEGFR-2 expression, upregulated occludin expression, inhibited the migration and proliferation of HRCECs, and inhibited the formation of TLSs. Thus, HESR1 plays a key role in the finely tuned network of molecules involved in the regulation of retinal vascular homeostasis. HESR1 seems to inhibit the vessel-promoting effects of VEGF, shift endothelial cells from a proliferative state to a quiescent state, and restore normal vessel structures. Expression of the HESR1 gene in retinal vascular endothelial cells may protect retinal blood vessels and may be useful in the treatment of diseases involving damage to the retinal vasculature, including diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion.
Li
Bin
B
State Key Laboratory of Ophthalmology, Zhongshan Opthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Tang
Shi-Bo
SB
Hu
Jie
J
Gao
Yi
Y
Zhang
Ge
G
Lin
Shao-Fen
SF
Chen
Jian-Hong
JH
Li
Bao-Jin
BJ
D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D062793:Occludin; D034741:RNA, Small Interfering / Q000235:genetics; D015861:Retinal Neovascularization / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D062793:Occludin; D034741:RNA, Small Interfering; D040301:Vascular Endothelial Growth Factor Receptor-2; C485631:HEY1 protein, human; C568985:OCLN protein, human