Related Transcriptional Enhancer Factor 1 Increases Endothelial-Dependent Microvascular Relaxation and Proliferation
| Autor: | Isabel Lubenec, Yuhong Liu, Ping He, Jue-Lon Shie, Angela F. Messmer-Blust, Jian Li, Qinhui Song, Cuili Zhang, Frank W. Sellke |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Nitric Oxide Synthase Type III
Physiology Muscle Proteins Vasodilation Biology DNA-binding protein Transcriptional regulation Animals Humans Receptor Fibroblast Growth Factor Type 1 Enhancer Promoter Regions Genetic Transcription factor Cells Cultured Cell Proliferation Cell growth Fibroblast growth factor receptor 1 TEA Domain Transcription Factors Molecular biology Cell biology DNA-Binding Proteins Microvessels Cattle Endothelium Vascular Signal transduction Cardiology and Cardiovascular Medicine Research Paper Signal Transduction Transcription Factors |
| Popis: | Objective: Related transcriptional enhancer factor 1 (RTEF-1) is a key transcriptional regulator in endothelial function. In this study, we investigated a possible role for RTEF-1 in the regulation of microvascular relaxation and the underlying mechanism involved. Activation of fibroblast growth factor receptor 1 (FGFR1) by FGFs increases vasodilation, although transcriptional control of the molecular mechanisms underlying FGFR1 is still unclear. Materials and Methods: We demonstrated that RTEF-1 stimulated FGFR1 expression at the transcriptional level, specifically an area including Sp1 elements, as evidenced by promoter assays. Additionally, RTEF-1 increased FGFR1 mRNA and protein expression in vitro and in VE-cadherin-promoted RTEF-1 (VE-Cad/RTEF-1) transgenic mice, whereas RTEF-1 siRNA blocked the upregulation of FGFR1 expression. Furthermore, increased endothelial-dependent microvessel relaxation was observed in the coronary arteries of VE-Cad/RTEF-1 mice, and increased proliferation was observed in RTEF-1-overexpressing cells, both of which correlated to increased FGF/FGFR1 signaling and endothelial nitric oxide synthase (eNOS) upregulation. Our results indicate that RTEF-1 acts as a transcriptional stimulator of FGFR1 and is involved in FGF pathways by increasing microvessel dilatation via eNOS. Conclusions: These findings suggest that RTEF-1 plays an important role in FGFR1- stimulated vasodilatation. Understanding the effect of RTEF-1 in microvessel relaxation may provide beneficial knowledge in improving treatments in regards to ischemic vascular disorders. |
| Databáze: | OpenAIRE |
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