Endothelial cells require related transcription enhancer factor-1 for cell-cell connections through the induction of gap junction proteins
| Autor: | Jian Li, Melissa J. Philbrick, Angela F. Messmer-Blust, Xiaoxiao Song, Heather S. Duffy, Ming Xu, Yi Jin, Ping He, Xiaojin An, Jiaping Wu, Brittany L. Cully |
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| Rok vydání: | 2012 |
| Předmět: |
Cell signaling
Cell- och molekylärbiologi Connexin Muscle Proteins Neovascularization Physiologic Cell Communication Biology Connexins Mice Animals Humans Enhancer Transcription factor Cells Cultured Cell Aggregation Matrigel Gap junction Endothelial Cells TEA Domain Transcription Factors Cell aggregation Cell biology Endothelial stem cell DNA-Binding Proteins Connexin 43 Cardiology and Cardiovascular Medicine Cell and Molecular Biology Transcription Factors |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 32(8) |
| ISSN: | 1524-4636 |
| Popis: | 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. Methods and 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. Conclusion— These findings provide novel insights into the transcriptional control of endothelial function in the coordination of cell–cell connections. |
| Databáze: | OpenAIRE |
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