Therapeutic modulation of RNA-binding protein Rbm38 facilitates re-endothelialization after arterial injury

Autor: Angelika Pfanne, Kristina Sonnenschein, Andreas Pich, Johann Bauersachs, Jan Fiedler, Robert Geffers, Thomas Thum, Saskia Mitzka, Annette Just
Přispěvatelé: HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Time Factors
Endothelium
Physiology
Apoptosis
Vascular injury
Umbilical vein
03 medical and health sciences
0302 clinical medicine
Re-Epithelialization
In vivo
Cell Movement
Physiology (medical)
microRNA
medicine
Human Umbilical Vein Endothelial Cells
RNA Precursors
Gene silencing
Animals
Humans
3' Untranslated Regions
vascular injury
Cell Proliferation
Vascular Pathophysiology
Binding Sites
Cell growth
business.industry
RNA-binding protein Rbm38
Endothelial Cells
RNA-Binding Proteins
Original Articles
re-endothelialization
Re-endothelialization
Endothelial stem cell
Mice
Inbred C57BL
Disease Models
Animal
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
HEK293 Cells
030220 oncology & carcinogenesis
Cancer research
Cardiology and Cardiovascular Medicine
business
Carotid Artery Injuries
Signal Transduction
Zdroj: Cardiovascular Research
Cardiovascular research
ISSN: 1755-3245
Popis: Aims Delayed re-endothelialization after balloon angioplasty in patients with coronary or peripheral artery disease impairs vascular healing and leads to neointimal proliferation. In the present study, we examined the effect of RNA-binding motif protein 38 (Rbm38) during re-endothelialization in a murine model of experimental vascular injury. Methods and results Left common carotid arteries of C57BL/6 mice were electrically denudated and endothelial regeneration was evaluated. Profiling of RNA-binding proteins revealed dysregulated expression of Rbm38 in the denudated and regenerated areas. We next tested the importance of Rbm38 in human umbilical vein endothelial cells (HUVECS) and analysed its effects on cellular proliferation, migration and apoptosis. Rbm38 silencing in vitro demonstrated important beneficial functional effects on migratory capacity and proliferation of endothelial cells. In vivo, local silencing of Rbm38 also improved re-endothelialization of denuded carotid arteries. Luciferase reporter assay identified miR-98 and let-7f to regulate Rbm38 and the positive proliferative properties of Rbm38 silencing in vitro and in vivo were mimicked by therapeutic overexpression of these miRNAs. Conclusion The present data identified Rbm38 as an important factor of the regulation of various endothelial cell functions. Local inhibition of Rbm38 as well as overexpression of the upstream regulators miR-98 and let-7f improved endothelial regeneration in vivo and thus may be a novel therapeutic entry point to avoid endothelial damage after balloon angioplasty.
Databáze: OpenAIRE
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