Endothelial angiogenesis is directed by RUNX1T1-regulated VEGFA, BMP4 and TGF-β2 expression.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Gene Expression Regulation* ; Neovascularization, Physiologic*; Bone Morphogenetic Protein 4/*metabolism ; Human Umbilical Vein Endothelial Cells/*metabolism ; Proto-Oncogene Proteins/*metabolism ; Transcription Factors/*metabolism ; Transforming Growth Factor beta2/*metabolism ; Vascular Endothelial Growth Factor A/*metabolism; Animals ; Blood Vessels/physiology ; Fetal Blood/cytology ; Gene Knockout Techniques ; Human Umbilical Vein Endothelial Cells/cytology ; Humans ; Mice ; Proto-Oncogene Proteins/deficiency ; Proto-Oncogene Proteins/genetics ; RUNX1 Translocation Partner 1 Protein ; Transcription Factors/deficiency ; Transcription Factors/genetics

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.

J Nanosci Nanotechnol. 2015 Jun;15(6):4239-44. (PMID: 26369035)
Blood. 1996 Sep 1;88(5):1813-23. (PMID: 8781439)
World J Stem Cells. 2014 Jul 26;6(3):355-66. (PMID: 25126384)
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517)
Neurosci Lett. 2010 Apr 19;474(1):46-51. (PMID: 20214951)
Gene Expr Patterns. 2002 Nov;2(1-2):93-7. (PMID: 12617844)
Am J Reprod Immunol. 1997 Jan;37(1):21-9. (PMID: 9138450)
Anticancer Res. 2016 Oct;36(10 ):5257-5263. (PMID: 27798886)
Mol Cell Biol. 2002 Aug;22(15):5506-17. (PMID: 12101243)
Circ Res. 2013 Apr 26;112(9):1272-87. (PMID: 23620236)
Front Biosci (Landmark Ed). 2012 Jan 01;17:1120-39. (PMID: 22201794)
Nat Genet. 2004 Jul;36(7):687-93. (PMID: 15220918)
Development. 2008 Jan;135(2):401-10. (PMID: 18156164)
FASEB J. 2015 Jul;29(7):3085-99. (PMID: 25854700)
Exp Hematol. 2007 Jun;35(6):978-88. (PMID: 17533052)
PLoS One. 2014 Sep 25;9(9):e107127. (PMID: 25254487)
Science. 1997 Feb 14;275(5302):964-7. (PMID: 9020076)
J Vasc Surg. 2006 Jan;43(1):134-41. (PMID: 16414400)
Nature. 1997 Apr 17;386(6626):671-4. (PMID: 9109485)
J Clin Invest. 2000 Jun;105(11):1527-36. (PMID: 10841511)
Mol Cell Biol. 2004 Nov;24(22):9863-72. (PMID: 15509789)
Atherosclerosis. 2010 Jul;211(1):297-302. (PMID: 20171637)
Int J Endocrinol. 2015;2015:521381. (PMID: 26788058)
PLoS One. 2014 Feb 19;9(2):e89326. (PMID: 24586690)
J Exp Med. 2007 Dec 24;204(13):3257-69. (PMID: 18070934)
Dev Biol. 1996 Jul 10;177(1):332-46. (PMID: 8660899)
Nat Rev Mol Cell Biol. 2011 Aug 23;12(9):551-64. (PMID: 21860391)
Microvasc Res. 2010 Sep;80(2):188-94. (PMID: 20362592)
Endocrinology. 2002 Apr;143(4):1545-53. (PMID: 11897714)
Biochemistry (Mosc). 2008 Jul;73(7):751-62. (PMID: 18707583)
Cytokine Growth Factor Rev. 2005 Apr;16(2):159-78. (PMID: 15863032)
Circ Res. 2010 Sep 3;107(5):602-14. (PMID: 20634489)
J Exp Zool. 1989 Aug;251(2):224-31. (PMID: 2671254)
Int J Cancer. 2012 Aug 15;131(4):834-43. (PMID: 21918972)
Toxicol Pathol. 2009 Jun;37(4):395-414. (PMID: 19359541)
Mech Dev. 2002 Nov;119(1):35-44. (PMID: 12385752)
Indian J Endocrinol Metab. 2012 Nov;16(6):918-30. (PMID: 23226636)
Nature. 1996 Apr 4;380(6573):439-42. (PMID: 8602242)
Mol Cell Biol. 2000 Mar;20(6):2075-86. (PMID: 10688654)
Dev Dyn. 1995 Nov;204(3):228-39. (PMID: 8573716)
Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2246-54. (PMID: 16123328)
J Pathol. 2009 May;218(1):7-29. (PMID: 19309025)
Arterioscler Thromb Vasc Biol. 2014 Apr;34(4):857-69. (PMID: 24558106)
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3287-92. (PMID: 19966309)
Gene. 1998 May 28;212(1):103-9. (PMID: 9661669)
Toxicol Lett. 2013 Apr 26;218(3):224-34. (PMID: 23403272)
Genes Dev. 1995 Sep 1;9(17):2105-16. (PMID: 7657163)
EMBO J. 1993 Jul;12(7):2715-21. (PMID: 8334990)
Nature. 2011 May 19;473(7347):298-307. (PMID: 21593862)
PLoS One. 2014 May 27;9(5):e98070. (PMID: 24865854)
Leukemia. 1994 Oct;8(10):1780-4. (PMID: 7523801)
PLoS Genet. 2014 Oct 16;10(10):e1004645. (PMID: 25330008)
J Cell Biol. 2012 Jun 11;197(6):837-49. (PMID: 22665518)
J Mol Med (Berl). 2013 Mar;91(3):285-95. (PMID: 23371317)
Mol Cell Biol. 2001 Aug;21(16):5658-66. (PMID: 11463846)
BMC Genomics. 2013 Mar 15;14:182. (PMID: 23496821)
Gene. 2017 Jun 5;615:35-40. (PMID: 28322996)
Genome Res. 2003 Mar;13(3):476-84. (PMID: 12618378)
J Vis Exp. 2013 Mar 16;(73):e50062. (PMID: 23524912)
Curr Opin Hematol. 2009 May;16(3):195-201. (PMID: 19346940)
Dev Biol. 2005 Oct 15;286(2):507-20. (PMID: 16168983)
Mol Cell Biol. 2001 Oct;21(19):6470-83. (PMID: 11533236)
Exp Biol Med (Maywood). 2007 Jun;232(6):833-43. (PMID: 17526776)
Dev Biol. 2005 Feb 1;278(1):22-34. (PMID: 15649458)
Biomaterials. 2015 Jan;37:164-73. (PMID: 25453947)

0 (BMP4 protein, human)
0 (Bone Morphogenetic Protein 4)
0 (Proto-Oncogene Proteins)
0 (RUNX1 Translocation Partner 1 Protein)
0 (RUNX1T1 protein, human)
0 (Transcription Factors)
0 (Transforming Growth Factor beta2)
0 (VEGFA protein, human)
0 (Vascular Endothelial Growth Factor A)

Date Created: 20170623 Date Completed: 20170918 Latest Revision: 20181113

20240513

PMC5481149

10.1371/journal.pone.0179758

28640846