Endothelial angiogenesis is directed by RUNX1T1-regulated VEGFA, BMP4 and TGF-β2 expression
| Autor: | Tse Shun Huang, Chuan Chi Shih, Wei Lun Hwang, Wen Wei Lin, Chi Hung Lin, Ko Hsun Liao, Oscar K. Lee, Muh Hwa Yang, Chen Li Chien, Hsin Chuan Chang, Shung Haur Yang, Te Chia Feng, Shing-Jyh Chang |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Vascular Endothelial Growth Factor A Embryology Angiogenesis Physiology lcsh:Medicine Gene Expression Bone Morphogenetic Protein 4 Cardiovascular Physiology Epithelium Neovascularization Gene Knockout Techniques Mice 0302 clinical medicine RUNX1 Translocation Partner 1 Protein Animal Cells Medicine and Health Sciences Enzyme assays Colorimetric assays lcsh:Science Bioassays and physiological analysis Regulation of gene expression Multidisciplinary MTT assay Stem Cells Heart Animal Models Fetal Blood Cell biology Vascular endothelial growth factor A Bone morphogenetic protein 4 Experimental Organism Systems 030220 oncology & carcinogenesis medicine.symptom Cellular Types Anatomy Research Article Neovascularization Physiologic Mouse Models Biology Research and Analysis Methods 03 medical and health sciences Transforming Growth Factor beta2 Model Organisms Proto-Oncogene Proteins medicine Genetics Human Umbilical Vein Endothelial Cells Animals Humans Progenitor cell lcsh:R Embryos RUNX1T1 Biology and Life Sciences Endothelial Cells Epithelial Cells Cell Biology Embryonic stem cell 030104 developmental biology Biological Tissue Gene Expression Regulation Biochemical analysis Cardiovascular Anatomy Blood Vessels lcsh:Q Developmental Biology Transcription Factors |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 6, p e0179758 (2017) |
| ISSN: | 1932-6203 |
| Popis: | Tissue angiogenesis is intimately regulated during embryogenesis and postnatal development. Defected angiogenesis contributes to aberrant development and is the main complication associated with ischemia-related diseases. We previously identified the increased expression of RUNX1T1 in umbilical cord blood-derived endothelial colony-forming cells (ECFCs) by gene expression microarray. However, the biological relevance of RUNX1T1 in endothelial lineage is not defined clearly. Here, we demonstrate RUNX1T1 regulates the survival, motility and tube forming capability of ECFCs and EA.hy926 endothelial cells by loss-and gain-of function assays, respectively. Second, embryonic vasculatures and quantity of bone marrow-derived angiogenic progenitors are found to be reduced in the established Runx1t1 heterozygous knockout mice. Finally, a central RUNX1T1-regulated signature is uncovered and VEGFA, BMP4 as well as TGF-β2 are demonstrated to mediate RUNX1T1-orchested angiogenic activities. Taken together, our results reveal that RUNX1T1 serves as a common angiogenic driver for vaculogenesis and functionality of endothelial lineage cells. Therefore, the discovery and application of pharmaceutical activators for RUNX1T1 will improve therapeutic efficacy toward ischemia by promoting neovascularization. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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