Evidence map›Paper›PMID 25795725›Full record

ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015

c-Abl mediated tyrosine phosphorylation of paxillin regulates LPS-induced endothelial dysfunction and lung injury.

Panfeng Fu, Peter V Usatyuk, Abhishek Lele, Anantha Harijith, Carol C Gregorio, Joe G N Garcia, Ravi Salgia, Viswanathan Natarajan

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

28 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
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  7. siRNA-MediatedInternational journal of molecular sciences · 2023
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  17. Cortical Actin Dynamics in Endothelial Permeability.Current topics in membranes · 2018
    Article
  18. American journal of physiology. Heart and circulatory physiology · 2017
    Article
  19. Article
  20. Review
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 3 institutions in 1 country.

Panfeng FuDepartment of Pharmacology, University of Illinois, Chicago, Illinois; pfu@uic.edu.
Peter V UsatyukDepartment of Pharmacology, University of Illinois, Chicago, Illinois;
Abhishek LeleDepartment of Pharmacology, University of Illinois, Chicago, Illinois;
Anantha HarijithDepartment of Pediatrics, University of Illinois, Chicago, Illinois;
Carol C GregorioDepartment of Cellular and Molecular Medicine, The University of Arizona College of Medicine, Tucson, Arizona;
Joe G N GarciaDepartment of Medicine, The University of Arizona College of Medicine, Tucson, Arizona; and.
Ravi SalgiaDepartment of Medicine, University of Chicago, Chicago, Illinois.
Viswanathan NatarajanDepartment of Pharmacology, University of Illinois, Chicago, Illinois; Department of Medicine, College of Medicine, University of Illinois, Chicago, Illinois;
University of Illinois Chicago · USUniversity of Arizona · USUniversity of Chicago · US

Funding

Tissue Culture Biomechanical CoreP01HL058064 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI LAL, RATNESHWAR · 1998 to 2012
$27.8M
Structure-Function Analysis of nmMLCK in EC Barrier ResponsesP01HL126609 · NHLBI · UNIVERSITY OF FLORIDA · PI STEVEN M DUDEK · 2016 to 2026
$24.4M
Therapeutic Potential of FTY720 Analogues in Lung InjuryP01HL098050 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI NATARAJAN, VISWANATHAN · 2011 to 2015
$10.9M
NHLBI NIH HHS P01 HL058064NHLBI NIH HHS P01 HL098050NHLBI NIH HHS P01 HL126609NHLBI NIH HHS P01HL58064NHLBI NIH HHS P01HL98050
6 · The paper itself

Abstract

Paxillin is phosphorylated at multiple residues; however, the role of tyrosine phosphorylation of paxillin in endothelial barrier dysfunction and acute lung injury (ALI) remains unclear. We used siRNA and site-specific nonphosphorylable mutants of paxillin to abrogate the function of paxillin to determine its role in lung endothelial permeability and ALI. In vitro, lipopolysaccharide (LPS) challenge of human lung microvascular endothelial cells (HLMVECs) resulted in enhanced tyrosine phosphorylation of paxillin at Y31 and Y118 with no significant change in Y181 and significant barrier dysfunction. Knockdown of paxillin with siRNA attenuated LPS-induced endothelial barrier dysfunction and destabilization of VE-cadherin. LPS-induced paxillin phosphorylation at Y31 and Y118 was mediated by c-Abl tyrosine kinase, but not by Src and focal adhesion kinase. c-Abl siRNA significantly reduced LPS-induced endothelial barrier dysfunction. Transfection of HLMVECs with paxillin Y31F, Y118F, and Y31/118F double mutants mitigated LPS-induced barrier dysfunction and VE-cadherin destabilization. In vivo, the c-Abl inhibitor AG957 attenuated LPS-induced pulmonary permeability in mice. Together, these results suggest that c-Abl mediated tyrosine phosphorylation of paxillin at Y31 and Y118 regulates LPS-mediated pulmonary vascular permeability and injury.

Indexed as

Acute Lung InjuryAnimalsAntigens, CDCadherin 5CadherinsCapillary PermeabilityCells, CulturedEndothelium, VascularFocal Adhesion Kinase 1Gene Knockdown TechniquesHumansLipopolysaccharidesMaleMicePaxillinPhosphorylationAntigens, CDCadherin 5CadherinsFocal Adhesion Kinase 1LipopolysaccharidesPaxillinProto-Oncogene Proteins c-ablPTK2 protein, humanPtk2 protein, mousePXN protein, humanPxn protein, mousetyrphostin AG957Tyrphostinsc-Ablcytoskeletonendothelial dysfunctionlipopolysaccharidepaxillinpermeabilitytyrosine kinase

Identifiers

PMID25795725
PMCPMC4437005
OpenAlexW2028809936

What OpenQuestion holds

Textmetadata
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.