Characterization of regulatory mechanisms mediating microRNA selection, packaging and transfer via microvesicles

• Applicant: Privatdozent Dr. Felix Jansen
• Subject Area: Cardiology, Angiology
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 349825282

• Final Report Year: 2022

Final Report Abstract

Mithilfe des hier beschriebenen Antrags war es möglich, miR-Verpackungsmechanismen von Zellen in Vesikel zu beschreiben. Als Schlüsselprotein bei der Regulation der miR-Verpackung konnte HnRNPU charakterisiert werden. Die Regulation von HnRNPU hatte direkten Einfluss auf die Spiegel von spezifischen miRs (zB miR130a) in Zellen und Vesikeln. Darüberhinaus könnten wir die Rolle von EV-transferierter miR-126 in VSMC charakterisieren. Der Transfer von miR-126 von Endothelzellen in VSMCs führte zu einer verminderten Proliferation und Migration in einem LRP6-ßCatenin abhängigen Weg der VSMCs.

Publications

• Endothelial microparticle-promoted inhibition of vascular remodeling is abrogated under hyperglycaemic conditions. Journal of Molecular and Cellular Cardiology, 112, 91-94.
  Jansen, Felix; Zietzer, Andreas; Stumpf, Tobias; Flender, Anna; Schmitz, Theresa; Nickenig, Georg & Werner, Nikos
  
• Extracellular Vesicles in Cardiovascular Disease. Circulation Research, 120(10), 1649-1657.
  Jansen, Felix; Nickenig, Georg & Werner, Nikos
  
• Atherosclerotic Conditions Promote the Packaging of Functional MicroRNA-92a-3p Into Endothelial Microvesicles. Circulation Research, 124(4), 575-587.
  Liu, Yangyang; Li, Qian; Hosen, Mohammed Rabiul; Zietzer, Andreas; Flender, Anna; Levermann, Paula; Schmitz, Theresa; Frühwald, Daniel; Goody, Philip; Nickenig, Georg; Werner, Nikos & Jansen, Felix
  
• Sodium thiocyanate treatment attenuates atherosclerotic plaque formation and improves endothelial regeneration in mice. PLOS ONE, 14(4), e0214476.
  Zietzer, Andreas; Niepmann, Sven Thomas; Camara, Bakary; Lenart, Monika Anna; Jansen, Felix; Becher, Marc Ulrich; Andrié, René; Nickenig, Georg & Tiyerili, Vedat
  
• MicroRNA-mediated vascular intercellular communication is altered in chronic kidney disease. Cardiovascular Research, 118(1), 316-333.
  Zietzer, Andreas; Steffen, Eva; Niepmann, Sven; Düsing, Philip; Hosen, Mohammed Rabiul; Liu, Weiyi; Jamme, Paul; Al-Kassou, Baravan; Goody, Philipp Roger; Zimmer, Sebastian; Reiners, Katrin S.; Pfeifer, Alexander; Böhm, Michael; Werner, Nikos; Nickenig, Georg & Jansen, Felix
  
• The RNA‐binding protein hnRNPU regulates the sorting of microRNA‐30c‐5p into large extracellular vesicles. Journal of Extracellular Vesicles, 9(1).
  Zietzer, Andreas; Hosen, Mohammed Rabiul; Wang, Han; Goody, Philip Roger; Sylvester, Marc; Latz, Eicke; Nickenig, Georg; Werner, Nikos & Jansen, Felix
  
• Activation of neutral sphingomyelinase 2 through hyperglycemia contributes to endothelial apoptosis via vesicle-bound intercellular transfer of ceramides. Cellular and Molecular Life Sciences, 79(1).
  Zietzer, Andreas; Jahnel, Alina Lisann; Bulic, Marko; Gutbrod, Katharina; Düsing, Philip; Hosen, Mohammed Rabiul; Dörmann, Peter; Werner, Nikos; Nickenig, Georg & Jansen, Felix
  
• CAD increases the long noncoding RNA PUNISHER in small extracellular vesicles and regulates endothelial cell function via vesicular shuttling. Molecular Therapy - Nucleic Acids, 25, 388-405.
  Hosen, Mohammed Rabiul; Li, Qian; Liu, Yangyang; Zietzer, Andreas; Maus, Katharina; Goody, Philip; Uchida, Shizuka; Latz, Eicke; Werner, Nikos; Nickenig, Georg & Jansen, Felix