Evidence map›Paper›PMID 26538583›Full record

ArticleCirculation2016

Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and Central Nervous System Homeostasis.

Khiem A Tran, Xianming Zhang, Dan Predescu, Xiaojia Huang, Roberto F Machado, Joachim R Göthert, Asrar B Malik, Tibor Valyi-Nagy, You-Yang Zhao

Open access · bronzeAbstract readVideo-Audio Media
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

147 citing papers in PubMed, 1 synthesis or guideline pooled it, 217 citations in OpenAlex.

  1. Pooled it
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  7. Alzheimer disease protection from the periphery.Nature reviews. Neurology · 2026
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  13. Observational
  14. Network Pharmacology, Molecular Docking, andCurrent topics in medicinal chemistry · 2026
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  20. Article

87 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Khiem A TranFrom Department of Pharmacology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Center for Lung and Vascular Biology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Department of Medicine (R.F.M.), and Department of Pathology (T.V.-N.), University of Illinois College of Medicine, Chicago; Department of Pharmacology, Rush University, Chicago, IL (D.P.); and Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany (J.R.G.).
Xianming ZhangFrom Department of Pharmacology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Center for Lung and Vascular Biology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Department of Medicine (R.F.M.), and Department of Pathology (T.V.-N.), University of Illinois College of Medicine, Chicago; Department of Pharmacology, Rush University, Chicago, IL (D.P.); and Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany (J.R.G.).
Dan PredescuFrom Department of Pharmacology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Center for Lung and Vascular Biology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Department of Medicine (R.F.M.), and Department of Pathology (T.V.-N.), University of Illinois College of Medicine, Chicago; Department of Pharmacology, Rush University, Chicago, IL (D.P.); and Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany (J.R.G.).
Xiaojia HuangFrom Department of Pharmacology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Center for Lung and Vascular Biology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Department of Medicine (R.F.M.), and Department of Pathology (T.V.-N.), University of Illinois College of Medicine, Chicago; Department of Pharmacology, Rush University, Chicago, IL (D.P.); and Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany (J.R.G.).
Roberto F MachadoFrom Department of Pharmacology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Center for Lung and Vascular Biology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Department of Medicine (R.F.M.), and Department of Pathology (T.V.-N.), University of Illinois College of Medicine, Chicago; Department of Pharmacology, Rush University, Chicago, IL (D.P.); and Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany (J.R.G.).
Joachim R GöthertFrom Department of Pharmacology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Center for Lung and Vascular Biology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Department of Medicine (R.F.M.), and Department of Pathology (T.V.-N.), University of Illinois College of Medicine, Chicago; Department of Pharmacology, Rush University, Chicago, IL (D.P.); and Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany (J.R.G.).
Asrar B MalikFrom Department of Pharmacology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Center for Lung and Vascular Biology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Department of Medicine (R.F.M.), and Department of Pathology (T.V.-N.), University of Illinois College of Medicine, Chicago; Department of Pharmacology, Rush University, Chicago, IL (D.P.); and Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany (J.R.G.).
Tibor Valyi-NagyFrom Department of Pharmacology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Center for Lung and Vascular Biology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Department of Medicine (R.F.M.), and Department of Pathology (T.V.-N.), University of Illinois College of Medicine, Chicago; Department of Pharmacology, Rush University, Chicago, IL (D.P.); and Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany (J.R.G.).
You-Yang ZhaoFrom Department of Pharmacology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Center for Lung and Vascular Biology (K.A.T., X.Z., X.H., A.B.M., Y.Y.Z), Department of Medicine (R.F.M.), and Department of Pathology (T.V.-N.), University of Illinois College of Medicine, Chicago; Department of Pharmacology, Rush University, Chicago, IL (D.P.); and Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany (J.R.G.). yyzhao@uic.edu.
Rush University · US

Funding

TRPC6 Regulation of Lung Endothelial Barrier FunctionP01HL060678 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MALIK, ASRAR B. · 2000 to 2020
$40.1M
Trpm2 Regulation of Phagocyte Bactericidal Activity and Resolution of Lung InjuryP01HL077806 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MALIK, ASRAR B. · 2005 to 2019
$27.0M
TRAINING PROGRAM IN LUNG BIOLOGY AND PATHOBIOLOGYT32HL007829 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DOLLY MEHTA · 1995 to 2026
$15.6M
Vascular Targeting Genomic & Genetic Strategies for Acute Chest SyndromeR01HL111656 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI Roberto F. Machado · 2013 to 2026
$7.9M
Repair mechanisms of sepsis induced endothelial dysfunction and lung injuryR01HL125350 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MALIK, ASRAR B., ZHAO, YOU-YANG · 2014 to 2018
$3.2M
FoxM1 regulates endothelial repair following lung vascular injuryR01HL085462 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI ZHAO, YOU-YANG · 2007 to 2011
$2.0M
Novel Signalings and Molecular Targets Of Endothelial Regeneration In Aging LungR01HL123957 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI ZHAO, YOU-YANG · 2014 to 2018
$2.0M
FoxM1 regulates endothelial repair following lung vascular injuryR56HL085462 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI ZHAO, YOU-YANG · 2013 to 2013
$399k
NHLBI NIH HHS P01 HL060678NHLBI NIH HHS P01 HL077806NHLBI NIH HHS P01HL077806NHLBI NIH HHS R01 HL085462NHLBI NIH HHS R01 HL111656NHLBI NIH HHS R01 HL123957NHLBI NIH HHS R01HL123957NHLBI NIH HHS R01 HL125350NHLBI NIH HHS R01HL125350NHLBI NIH HHS R56 HL085462NHLBI NIH HHS R56HL085462NHLBI NIH HHS T32 HL007829NHLBI NIH HHS T32HL007829
6 · The paper itself

Abstract

backgroundThe blood-brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. METHODS AND

resultsUsing a mouse model with tamoxifen-inducible endothelial cell-restricted disruption of ctnnb1 (iCKO), we show here that endothelial β-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear β-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients.

conclusionsThese results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation.

Indexed as

AdultAgedAnimalsAtaxiaBasal Gangliabeta CateninBlood-Brain BarrierBrainCerebral HemorrhageClaudin-1Claudin-3Crosses, GeneticCytokinesDown-RegulationEndothelial CellsFemalebeta CateninClaudin-1Claudin-3CLDN1 protein, humanCldn1 protein, mouseCldn3 protein, mouseCTNNB1 protein, humanCTNNB1 protein, mouseCytokinesblood–brain barrierbraincerebrovascular disordersendotheliumintracranial hemorrhages

Identifiers

PMID26538583
PMCPMC4814374
OpenAlexW2237670736

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.