Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: id:"swepub:oai:DiVA.org:uu-378993" > Fine-Tuning of Sox1...

1 of 1
Previous record
Next record
To hitlist

Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier

Corada, Monica (author): FIRC Inst Mol Oncol Fdn IFOM, Milan, Italy

Orsenigo, Fabrizio (author): FIRC Inst Mol Oncol Fdn IFOM, Milan, Italy

Bhat, Ganesh Parameshwar (author): Osped San Raffaele, Mol Neurobiol Lab, Div Neurosci, Milan, Italy

Conze, Lei Liu (author): Uppsala universitet,Vaskulärbiologi

Breviario, Ferruccio (author): FIRC Inst Mol Oncol Fdn IFOM, Milan, Italy

Cunha, Sara I. (author): Uppsala universitet,Vaskulärbiologi

Claesson-Welsh, Lena (author): Uppsala universitet,Vaskulärbiologi

Beznoussenko, Galina V. (author): FIRC Inst Mol Oncol Fdn IFOM, Milan, Italy

Mironov, Alexander A. (author): FIRC Inst Mol Oncol Fdn IFOM, Milan, Italy

Bacigaluppi, Marco (author): Osped San Raffaele, Neuroimmunol Unit, Div Neurosci, Inst Expt Neurol, Milan, Italy

Martino, Gianvito (author): Osped San Raffaele, Neuroimmunol Unit, Div Neurosci, Inst Expt Neurol, Milan, Italy

Pitulescu, Mara E. (author): Univ Munster, Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, Munster, Germany; Univ Munster, Fac Med, Munster, Germany

Adams, Ralf H. (author): Univ Munster, Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, Munster, Germany; Univ Munster, Fac Med, Munster, Germany

Magnusson, Peetra (author): Uppsala universitet,Vaskulärbiologi

Dejana, Elisabetta (author): Uppsala universitet,Vaskulärbiologi,FIRC Inst Mol Oncol Fdn IFOM, Milan, Italy; Univ Milan, Dept Oncol & Hematooncol, Milan, Italy

show less...

(creator_code:org_t)

2019
2019
English.
In: Circulation Research. - 0009-7330 .- 1524-4571. ; 124:4, s. 511-525

Related links:: https://doi.org/10.1...; show more...; https://uu.diva-port... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Rationale: The microvasculature of the central nervous system includes the blood-brain barrier (BBB), which regulates the permeability to nutrients and restricts the passage of toxic agents and inflammatory cells. Canonical Wnt/β-catenin signaling is responsible for the early phases of brain vascularization and BBB differentiation. However, this signal declines after birth, and other signaling pathways able to maintain barrier integrity at postnatal stage are still unknown.Objective: Sox17 (SRY [sex-determining region Y]-box 17) constitutes a major downstream target of Wnt/β-catenin in endothelial cells and regulates arterial differentiation. In the present article, we asked whether Sox17 may act downstream of Wnt/β-catenin in inducing BBB differentiation and maintenance.Methods and Results: Using reporter mice and nuclear staining of Sox17 and β-catenin, we report that although β-catenin signaling declines after birth, Sox17 activation increases and remains high in the adult. Endothelial-specific inactivation of Sox17 leads to increase of permeability of the brain microcirculation. The severity of this effect depends on the degree of BBB maturation: it is strong in the embryo and progressively declines after birth. In search of Sox17 mechanism of action, RNA sequencing analysis of gene expression of brain endothelial cells has identified members of the Wnt/β-catenin signaling pathway as downstream targets of Sox17. Consistently, we found that Sox17 is a positive inducer of Wnt/β-catenin signaling, and it acts in concert with this pathway to induce and maintain BBB properties. In vivo, inhibition of the β-catenin destruction complex or expression of a degradation-resistant β-catenin mutant, prevent the increase in permeability and retina vascular malformations observed in the absence of Sox17.Conclusions: Our data highlight a novel role for Sox17 in the induction and maintenance of the BBB, and they underline the strict reciprocal tuning of this transcription factor and Wnt/β-catenin pathway. Modulation of Sox17 activity may be relevant to control BBB permeability in pathological conditions.

Find in a library

Circulation Research (Search for host publication in LIBRIS)

To the university's database

1 of 1
Previous record
Next record
To hitlist

Find more in SwePub

By the author/editor: Corada, Monica; Orsenigo, Fabriz ...; Bhat, Ganesh Par ...; Conze, Lei Liu; Breviario, Ferru ...; Cunha, Sara I.; show more...; Claesson-Welsh, ...; Beznoussenko, Ga ...; Mironov, Alexand ...; Bacigaluppi, Mar ...; Martino, Gianvit ...; Pitulescu, Mara ...; Adams, Ralf H.; Magnusson, Peetr ...; Dejana, Elisabet ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

Articles in the publication: Circulation Rese ...

By the university: Uppsala University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se

Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier

Subject headings

Keyword

Publication and Content Type

Find in a library

To the university's database

Find more in SwePub

Search outside SwePub