| Autor: |
Ruiyuan Zheng, Kyle Moynahan, Theodoros Georgomanolis, Egor Pavlenko, Simon Geissen, Athanasia Mizi, Simon Grimm, Harshal Nemade, Rizwan Rehimi, Jil Bastigkeit, Jan-Wilm Lackmann, Matti Adam, Alvaro Rada-Iglesias, Peter Nuernberg, Anna Klinke, Simon Poepsel, Stephan Baldus, Argyris Papantonis, Yulia Kargapolova |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 27, Iss 2, Pp 108898- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2024.108898 |
| Popis: |
Summary: Myeloperoxidase (MPO) is an enzyme that functions in host defense. MPO is released into the vascular lumen by neutrophils during inflammation and may adhere and subsequently penetrate endothelial cells (ECs) coating vascular walls. We show that MPO enters the nucleus of ECs and binds chromatin independently of its enzymatic activity. MPO drives chromatin decondensation at its binding sites and enhances condensation at neighboring regions. It binds loci relevant for endothelial-to-mesenchymal transition (EndMT) and affects the migratory potential of ECs. Finally, MPO interacts with the RNA-binding factor ILF3 thereby affecting its relative abundance between cytoplasm and nucleus. This interaction leads to change in stability of ILF3-bound transcripts. MPO-knockout mice exhibit reduced number of ECs at scar sites following myocardial infarction, indicating reduced neovascularization. In summary, we describe a non-enzymatic role for MPO in coordinating EndMT and controlling the fate of endothelial cells through direct chromatin binding and association with co-factors. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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