The heparan sulfate proteoglycan agrin contributes to barrier properties of mouse brain endothelial cells by stabilizing adherens junctions

Steiner, Esther; Enzmann, Gaby; Lyck, Ruth; Lin, Shuo; Rüegg, Markus A; Kröger, Stephan; Engelhardt, Britta (2014). The heparan sulfate proteoglycan agrin contributes to barrier properties of mouse brain endothelial cells by stabilizing adherens junctions. Cell and tissue research, 358(2), pp. 465-479. Springer 10.1007/s00441-014-1969-7

[img]
Preview
Text
441_2014_Article_1969.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (7MB) | Preview

Barrier characteristics of brain endothelial cells forming the blood-brain barrier (BBB) are tightly regulated by cellular and acellular components of the neurovascular unit. During embryogenesis, the accumulation of the heparan sulfate proteoglycan agrin in the basement membranes ensheathing brain vessels correlates with BBB maturation. In contrast, loss of agrin deposition in the vasculature of brain tumors is accompanied by the loss of endothelial junctional proteins. We therefore wondered whether agrin had a direct effect on the barrier characteristics of brain endothelial cells. Agrin increased junctional localization of vascular endothelial (VE)-cadherin, β-catenin, and zonula occludens-1 (ZO-1) but not of claudin-5 and occludin in the brain endothelioma cell line bEnd5 without affecting the expression levels of these proteins. This was accompanied by an agrin-induced reduction of the paracellular permeability of bEnd5 monolayers. In vivo, the lack of agrin also led to reduced junctional localization of VE-cadherin in brain microvascular endothelial cells. Taken together, our data support the notion that agrin contributes to barrier characteristics of brain endothelium by stabilizing the adherens junction proteins VE-cadherin and β-catenin and the junctional protein ZO-1 to brain endothelial junctions.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Steiner, Esther; Enzmann, Gaby; Lyck, Ruth and Engelhardt, Britta

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0302-766X

Publisher:

Springer

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

07 Apr 2015 12:33

Last Modified:

21 Oct 2015 11:21

Publisher DOI:

10.1007/s00441-014-1969-7

PubMed ID:

25107608

BORIS DOI:

10.7892/boris.66331

URI:

https://boris.unibe.ch/id/eprint/66331

Actions (login required)

Edit item Edit item
Provide Feedback