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Arterioscler Thromb Vasc Biol. 2016 Apr;36(4):647-54. doi: 10.1161/ATVBAHA.115.307032. Epub 2016 Jan 28.

Evidence That Cingulin Regulates Endothelial Barrier Function In Vitro and In Vivo.

Author information

1
From the Skin and Endothelium Research Division (SERD), Department of Dermatology (K.S., S.R., M.G., H.P.F., R.F., P.P.), Core Facility Imaging (S.R., M.G.), Department of Cardiac Surgery (A.H.), Department of Medicine I, Institute of Cancer Research, Comprehensive Cancer Center (M.S.), Department of Surgery (C.B.), and Department of Dermatology (D.F.), Medical University of Vienna, Vienna, Austria; and Department of Cell Biology and Institute of Genetics and Genomics in Geneva, University of Geneva, Switzerland (S.C.).
2
From the Skin and Endothelium Research Division (SERD), Department of Dermatology (K.S., S.R., M.G., H.P.F., R.F., P.P.), Core Facility Imaging (S.R., M.G.), Department of Cardiac Surgery (A.H.), Department of Medicine I, Institute of Cancer Research, Comprehensive Cancer Center (M.S.), Department of Surgery (C.B.), and Department of Dermatology (D.F.), Medical University of Vienna, Vienna, Austria; and Department of Cell Biology and Institute of Genetics and Genomics in Geneva, University of Geneva, Switzerland (S.C.). Peter.Petzelbauer@meduniwien.ac.at.

Abstract

OBJECTIVE:

Cingulin is a cytoplasmic component of tight junctions. Although modulation of cingulin levels in cultured epithelial model systems has no significant effect on barrier function, evidence from cingulin knockout mice suggests that cingulin may be involved in the regulation of the behavior of epithelial or endothelial cells. Here, we investigate the role of cingulin in the barrier function of endothelial cells.

APPROACH AND RESULTS:

We show that cingulin is expressed in human endothelial cells of the skin, brain, and lung in vivo and in vitro. Endothelial cingulin colocalizes and coimmunoprecipitates with the tight junction proteins zonula occludens-1 and guanine nucleotide exchange factor-H1. Cingulin overexpression in human umbilical vein endothelial cell induces tight junction formation, increases transendothelial electric resistance, and strengthens barrier function for low and high molecular weight tracers. In contrast, cultured endothelial cells lacking cingulin are more permeable for low molecular weight tracers. In cingulin knockout mice, neurons of the area postrema and Purkinje cells show an increased uptake of small molecular weight tracers indicating decreased barrier function at these sites.

CONCLUSIONS:

We demonstrate that cingulin participates in the modulation of endothelial barrier function both in human cultured cells in vitro and in mouse brains in vivo. Understanding the role of cingulin in maintaining tight barriers in endothelia may allow developing new strategies for the treatment of vascular leak syndromes.

KEYWORDS:

capillary permeability; human umbilical vein endothelial cells; junctional adhesion molecules; mouse, mutant strain; vascular diseases

Comment in

PMID:
26821949
DOI:
10.1161/ATVBAHA.115.307032
[Indexed for MEDLINE]

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