Transcriptional control of endothelial tip cell function by Neuronal helix-loop-helix PAS (Per-ARNT-Sim) 4 -NPAS4-

• Applicant: Professor Dr. Martin Moser
• Subject Area: Cardiology, Angiology
• Term: from 2013 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 243746206

• Final Report Year: 2018

Final Report Abstract

In this project we characterized the transcription factor NPAS4 as an endothelial regulator of angiogenic sprouting and tip cell formation. NPAS4 is a novel transcription factor belonging to the HLH-PAS family. It was originally identified in drosophila and is necessary for tip cell fusion of the bronchial tubes in this species. Our data show for the first time that NPAS4 is expressed in endothelial cells. It is necessary and sufficient to induce endotheliacel cell sprouting and supports tip cell formation. We have located NPAS4 upstream of dll4, a notch signaling molecule and of VE- cadherin –both known to be involved in vascular sprouting. We have used several animal models to confirm our vitro findings. Thus NPAS4 is a novel transcription factor that controls endothelial cell sprouting and may serve as a target in future studies.

Publications

• Bone morphogenetic protein 4 regulates microRNAs miR-494 and miR-126-5p in control of endothelial cell function in angiogenesis. Thrombosis and haemostasis. 2017 Apr 03; 117: 734-749
  Esser JS, Saretzki E, Pankratz F, Engert B, Grundmann S, Bode C, Moser M and Zhou Q
  
• Bone Morphogenetic Protein-Modulator BMPER Regulates Endothelial Barrier Function. Inflammation. 2017 Apr; 40: 442-453
  Helbing T, Wiltgen G, Hornstein A, Brauers EZ, Arnold L, Bauer A, Esser JS, Diehl P, Grundmann S, Fink K, Patterson C, Bode C and Moser M
  
• The neuronal transcription factor NPAS4 is a strong inducer of sprouting angiogenesis and tip cell formation. Cardiovasc Res. 2017 Feb; 113: 222-223
  Esser JS, Charlet A, Schmidt M, Heck S, Allen A, Lother A, Epting D, Patterson C, Bode C and Moser M
  
• Cardiac Endothelial, Cell Transcriptome. Arterioscler Thromb Vasc Biol. 2018 Mar; 38(3):566-574
  Lother A, Bergemann S, Deng L, Moser M, Bode C, Hein L
  
• MicroRNA-100 Suppresses Chronic, Vascular Inflammation by Stimulation of Endothelial Autophagy. Circ Res. 2018 Feb, 2;122(3):417-432
  Pankratz F, Hohnloser C, Bemtgen X, Jaenich C, Kreuzaler S, Hoefer I, Pasterkamp G, Mastroianni J, Zeiser R, Smolka C, Schneider L, Martin J, Juschkat, M, Helbing T, Moser M, Bode C, Grundmann S