Evidence map›Paper›PMID 22213015›Full record

ArticleJournal of cellular physiology2012

VE-cadherin trans-interactions modulate Rac activation and enhancement of lung endothelial barrier by iloprost.

Anna A Birukova, Yufeng Tian, Oleksii Dubrovskyi, Noureddine Zebda, Nicolene Sarich, Xinyong Tian, Yingxiao Wang, Konstantin G Birukov

Abstract read
In one paragraph

Article in Journal of cellular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

33 citing papers in PubMed, 47 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Article
  5. Review
  6. Tunicamycin Protects against LPS-Induced Lung Injury.Pharmaceuticals (Basel, Switzerland) · 2022
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. VE-cadherin regulates migration inhibitory factor synthesis and release.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019
    Article
  12. Article
  13. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017
    Article
  14. Article
  15. In Development-A New Paradigm for Understanding Vascular Disease.Journal of cardiovascular pharmacology · 2017
    Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. Article
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

8 authors at 2 institutions in 1 country.

Anna A BirukovaLung Injury Center, Section of Pulmonary and Critical Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA. kbirukov@medicine.bsd.uchicago.edu
Yufeng Tian
Oleksii Dubrovskyi
Noureddine Zebda
Nicolene Sarich
Xinyong Tian
Yingxiao Wang
Konstantin G Birukov
University of Chicago · USUniversity of Illinois Urbana-Champaign · US

Funding

Tissue Culture Biomechanical CoreP01HL058064 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI LAL, RATNESHWAR · 1998 to 2012
$27.8M
Control of Lung Permeability by Oxidized PhospholipidsR01HL076259 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI BIRUKOV, KONSTANTIN · 2004 to 2023
$6.8M
Molecular control of lung endothelial barrier function in ALIR01HL087823 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI BIRUKOV, KONSTANTIN · 2008 to 2020
$4.6M
Microtubule-associated regulation of acute lung injuryR01HL107920 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI BIRUKOVA, ANNA · 2011 to 2019
$2.8M
Protective role of ANP in the models of acute lung injuryR01HL089257 · NHLBI · UNIVERSITY OF CHICAGO · PI BIRUKOVA, ANNA · 2009 to 2013
$1.9M
Microtubule-associated regulation of acute lung injuryR56HL107920 · NHLBI · UNIVERSITY OF CHICAGO · PI BIRUKOVA, ANNA · 2015 to 2015
$395k
NHLBI NIH HHS HL107920NHLBI NIH HHS HL58064NHLBI NIH HHS HL76259NHLBI NIH HHS HL87823NHLBI NIH HHS HL89257NHLBI NIH HHS P01 HL058064NHLBI NIH HHS R01 HL076259NHLBI NIH HHS R01 HL087823NHLBI NIH HHS R01 HL089257NHLBI NIH HHS R01 HL107920NHLBI NIH HHS R56 HL107920
6 · The paper itself

Abstract

Small GTPase Rac is important regulator of endothelial cell (EC) barrier enhancement by prostacyclin characterized by increased peripheral actin cytoskeleton and increased interactions between VE-cadherin and other adherens junction (AJ) proteins. This study utilized complementary approaches including siRNA knockdown, culturing in Ca(2+) -free medium, and VE-cadherin blocking antibody to alter VE-cadherin extracellular interactions to investigate the role of VE-cadherin outside-in signaling in modulation of Rac activation and EC barrier regulation by prostacyclin analog iloprost. Spatial analysis of Rac activation in pulmonary EC by FRET revealed additional spike in iloprost-induced Rac activity at the sites of newly formed cell-cell junctions. In contrast, disruption of VE-cadherin extracellular trans-interactions suppressed iloprost-activated Rac signaling and attenuated EC barrier enhancement and cytoskeletal remodeling. These inhibitory effects were associated with decreased membrane accumulation and activation of Rac-specific guanine nucleotide exchange factors (GEFs) Tiam1 and Vav2. Conversely, plating of pulmonary EC on surfaces coated with extracellular VE-cadherin domain further promoted iloprost-induced Rac signaling. In the model of thrombin-induced EC barrier recovery, blocking of VE-cadherin trans-interactions attenuated activation of Rac pathway during recovery phase and delayed suppression of Rho signaling and restoration of EC barrier properties. These results suggest that VE-cadherin outside-in signaling controls locally Rac activity stimulated by barrier protective agonists. This control is essential for maximal EC barrier enhancement and accelerated barrier recovery.

Indexed as

Adherens JunctionsAntibodiesAntigens, CDCadherin 5CadherinsCapillary PermeabilityCells, CulturedCytoskeletonEndothelial CellsEpoprostenolGuanine Nucleotide Exchange FactorsHumansIloprostIntercellular JunctionsLungProto-Oncogene Proteins c-vavAntibodiesAntigens, CDCadherin 5CadherinsEpoprostenolGuanine Nucleotide Exchange FactorsIloprostProto-Oncogene Proteins c-vavrac GTP-Binding ProteinsTIAM1 protein, humanT-Lymphoma Invasion and Metastasis-inducing Protein 1VAV2 protein, human

Identifiers

PMID22213015
PMCPMC3328640
OpenAlexW2135749644

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.