title: Evidence That Cingulin Regulates Endothelial Barrier Function In Vitro and In Vivo.
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.
  
  
  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.
authors.affiliation: 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.).
authors.forename: Klaudia
authors.initials: K
authors.lastname: Schossleitner
authors.affiliation: 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.).
authors.forename: Sabine
authors.initials: S
authors.lastname: Rauscher
authors.affiliation: 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.).
authors.forename: Marion
authors.initials: M
authors.lastname: Gröger
authors.affiliation: 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.).
authors.forename: Heinz Peter
authors.initials: HP
authors.lastname: Friedl
authors.affiliation: 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.).
authors.forename: Richard
authors.initials: R
authors.lastname: Finsterwalder
authors.affiliation: 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.).
authors.forename: Andreas
authors.initials: A
authors.lastname: Habertheuer
authors.affiliation: 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.).
authors.forename: Maria
authors.initials: M
authors.lastname: Sibilia
authors.affiliation: 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.).
authors.forename: Christine
authors.initials: C
authors.lastname: Brostjan
authors.affiliation: 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.).
authors.forename: Dagmar
authors.initials: D
authors.lastname: Födinger
authors.affiliation: 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.).
authors.forename: Sandra
authors.initials: S
authors.lastname: Citi
authors.affiliation: 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.
authors.forename: Peter
authors.initials: P
authors.lastname: Petzelbauer
mesh_terms: D000818:Animals; D031608:Area Postrema / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002199:Capillary Permeability; D049109:Cell Proliferation; D002478:Cells, Cultured; D062507:Claudin-5 / Q000378:metabolism; D017097:Electric Impedance; D042783:Endothelial Cells / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011689:Purkinje Cells / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors / Q000378:metabolism; D015398:Signal Transduction; D019108:Tight Junctions / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: C577356:ARHGEF2 protein, human; C061407:CGN protein, human; C107466:CLDN5 protein, human; C489227:Cgn protein, mouse; D062507:Claudin-5; D008565:Membrane Proteins; D008840:Microfilament Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein
keywords: capillary permeability; human umbilical vein endothelial cells; junctional adhesion molecules; mouse, mutant strain; vascular diseases