Loss of the transcription factor RBPJ induces disease-promoting properties in brain pericytes

Rodrigo Diéguez-Hurtado, Katsuhiro Kato, Benedetto Daniele Giaimo, Melina Nieminen-Kelhä, Hendrik Arf, Francesca Ferrante, Marek Bartkuhn, Tobias Zimmermann, M. Gabriele Bixel, Hanna M. Eilken, Susanne Adams, Tilman Borggrefe, Peter Vajkoczy () and Ralf H. Adams ()
Additional contact information
Rodrigo Diéguez-Hurtado: Max Planck Institute for Molecular Biomedicine
Katsuhiro Kato: Max Planck Institute for Molecular Biomedicine
Benedetto Daniele Giaimo: University of Giessen
Melina Nieminen-Kelhä: Charité-Universitätsmedizin
Hendrik Arf: Max Planck Institute for Molecular Biomedicine
Francesca Ferrante: University of Giessen
Marek Bartkuhn: University of Giessen
Tobias Zimmermann: University of Giessen
M. Gabriele Bixel: Max Planck Institute for Molecular Biomedicine
Hanna M. Eilken: Max Planck Institute for Molecular Biomedicine
Susanne Adams: Max Planck Institute for Molecular Biomedicine
Tilman Borggrefe: University of Giessen
Peter Vajkoczy: Charité-Universitätsmedizin
Ralf H. Adams: Max Planck Institute for Molecular Biomedicine

Nature Communications, 2019, vol. 10, issue 1, 1-19

Abstract: Abstract Sufficient vascular supply is indispensable for brain development and function, whereas dysfunctional blood vessels are associated with human diseases such as vascular malformations, stroke or neurodegeneration. Pericytes are capillary-associated mesenchymal cells that limit vascular permeability and protect the brain by preserving blood-brain barrier integrity. Loss of pericytes has been linked to neurodegenerative changes in genetically modified mice. Here, we report that postnatal inactivation of the Rbpj gene, encoding the transcription factor RBPJ, leads to alteration of cell identity markers in brain pericytes, increases local TGFβ signalling, and triggers profound changes in endothelial behaviour. These changes, which are not mimicked by pericyte ablation, imperil vascular stability and induce the acquisition of pathological landmarks associated with cerebral cavernous malformations. In adult mice, loss of Rbpj results in bigger stroke lesions upon ischemic insult. We propose that brain pericytes can acquire deleterious properties that actively enhance vascular lesion formation and promote pathogenic processes.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-10643-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10643-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-10643-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().