Endothelial cells require related transcription enhancer factor-1 for cell-cell connections through the induction of gap junction proteins.
OBJECTIVE
Capillary network formation represents a specialized endothelial cell function and is a prerequisite to establish a continuous vessel lumen. Formation of endothelial cell connections that form the vascular structure is regulated, at least in part, at the transcriptional level. We report here that related transcription enhancer factor-1 (RTEF-1) plays an important role in vascular structure formation.


RESULTS
Knockdown of RTEF-1 by small interfering RNA or blockage of RTEF-1 function by the transcription enhancer activators domain decreased endothelial connections in a Matrigel assay, whereas overexpression of RTEF-1 in endothelial cells resulted in a significant increase in cell connections and aggregation. In a model of oxygen-induced retinopathy, endothelial-specific RTEF-1 overexpressing mice had enhanced angiogenic sprouting and vascular structure remodeling, resulting in the formation of a denser and more highly interconnected superficial capillary plexus. Mechanistic studies revealed that RTEF-1 induced the expression of functional gap junction proteins including connexin 43, connexin 40, and connexin 37. Blocking connexin 43 function inhibited RTEF-1-induced endothelial cell connections and aggregation.


CONCLUSIONS
These findings provide novel insights into the transcriptional control of endothelial function in the coordination of cell-cell connections.
Institute of Molecular Medicine, Peking University, Beijing, China.
Xiaojin
X
An
Yi
Y
Jin
Melissa J
MJ
Philbrick
Jiaping
J
Wu
Angela
A
Messmer-Blust
Xiaoxiao
X
Song
Brittany L
BL
Cully
Ping
P
He
Ming
M
Xu
Heather S
HS
Duffy
Jian
J
Li
D000818:Animals; D002449:Cell Aggregation; D002450:Cell Communication; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics; D017630:Connexins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D018919:Neovascularization, Physiologic; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
D018031:Connexin 43; D017630:Connexins; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D000091262:TEA Domain Transcription Factors; C486309:TEAD4 protein, human; C101204:Tead4 protein, mouse; D014157:Transcription Factors