Evidence map›Paper›PMID 25518936›Full record

ArticleMolecular biology of the cell2015

Asef controls vascular endothelial permeability and barrier recovery in the lung.

Xinyong Tian, Yufeng Tian, Grzegorz Gawlak, Fanyong Meng, Yoshihiro Kawasaki, Tetsu Akiyama, Anna A Birukova

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
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

19 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Cortactin in Lung Cell Function and Disease.International journal of molecular sciences · 2022
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Temporal Profiling of Astrocyte Precursors Reveals Parallel Roles for Asef during Development and after Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016
    Article
  15. Article
  16. Using cultured endothelial cells to study endothelial barrier dysfunction: Challenges and opportunities.American journal of physiology. Lung cellular and molecular physiology · 2016
    Review
  17. Article
  18. Review
  19. 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

7 authors.

Xinyong TianSection of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637.
Yufeng TianSection of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637.
Grzegorz GawlakSection of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637.
Fanyong MengSection of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637.
Yoshihiro KawasakiLaboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
Tetsu AkiyamaLaboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
Anna A BirukovaSection of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637 abirukov@medicine.bsd.uchicago.edu.

Funding

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 HL89257NHLBI NIH HHS R01 HL089257NHLBI NIH HHS R01 HL107920NHLBI NIH HHS R56 HL107920
6 · The paper itself

Abstract

Increased levels of hepatocyte growth factor (HGF) in injured lungs may reflect a compensatory response to diminish acute lung injury (ALI). HGF-induced activation of Rac1 GTPase stimulates endothelial barrier protective mechanisms. This study tested the involvement of Rac-specific guanine nucleotide exchange factor Asef in HGF-induced endothelial cell (EC) cytoskeletal dynamics and barrier protection in vitro and in a two-hit model of ALI. HGF induced membrane translocation of Asef and stimulated Asef Rac1-specific nucleotide exchange activity. Expression of constitutively activated Asef mutant mimicked HGF-induced peripheral actin cytoskeleton enhancement. In contrast, siRNA-induced Asef knockdown or expression of dominant-negative Asef attenuated HGF-induced Rac1 activation evaluated by Rac-GTP pull down and FRET assay with Rac1 biosensor. Molecular inhibition of Asef attenuated HGF-induced peripheral accumulation of cortactin, formation of lamellipodia-like structures, and enhancement of VE-cadherin adherens junctions and compromised HGF-protective effect against thrombin-induced RhoA GTPase activation, Rho-dependent cytoskeleton remodeling, and EC permeability. Intravenous HGF injection attenuated lung inflammation and vascular leak in the two-hit model of ALI induced by excessive mechanical ventilation and thrombin signaling peptide TRAP6. This effect was lost in Asef(-/-) mice. This study shows for the first time the role of Asef in HGF-mediated protection against endothelial hyperpermeability and lung injury.

Indexed as

Cell Membrane PermeabilityAnimalsGene Knockdown TechniquesGuanine Nucleotide Exchange FactorsHepatocyte Growth FactorLungMicerac1 GTP-Binding ProteinRho Guanine Nucleotide Exchange FactorsRNA InterferenceSignal TransductionArhgef4 protein, mouseGuanine Nucleotide Exchange FactorsHepatocyte Growth Factorrac1 GTP-Binding ProteinRho Guanine Nucleotide Exchange Factors

Identifiers

PMID25518936
PMCPMC4325835

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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.