Evidence map›Paper›PMID 23296034›Full record

ArticleMicrovascular research2013

Endothelial barrier disruption and recovery is controlled by substrate stiffness.

Anna A Birukova, Xinyong Tian, Ivan Cokic, Yvonne Beckham, Margaret L Gardel, Konstantin G Birukov

Abstract readComparative Study
In one paragraph

Article in Microvascular research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

58 citing papers in PubMed, 94 citations in OpenAlex.

  1. [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026
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  3. Beyond classical collagen: basement membrane collagen IV in age-associated lung diseases.European respiratory review : an official journal of the European Respiratory Society · 2025
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  6. Anoctamin-1 is induced by TGF-β and contributes to lung myofibroblast differentiation.American journal of physiology. Lung cellular and molecular physiology · 2024
    Article
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  8. Review
  9. Mechanical regulation of the early stages of angiogenesis.Journal of the Royal Society, Interface · 2022
    Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Directing Multicellular Organization by Varying the Aspect Ratio of Soft Hydrogel Microwells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Article
  15. Review
  16. Review
  17. Article
  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

6 authors at 1 institution 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
Xinyong Tian
Ivan Cokic
Yvonne Beckham
Margaret L Gardel
Konstantin G Birukov
University of Chicago · US

Funding

Tissue Culture Biomechanical CoreP01HL058064 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI GARCIA, JOE G. N. · 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
2007 NIH Director's Pioneer Award Program (DP1)DP1OD003354 · OD · UNIVERSITY OF CHICAGO · PI GARDEL, MARGARET LISE · 2007 to 2011
$3.8M
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
NCCDPHP CDC HHS DP10D00354NHLBI NIH HHS HL058064NHLBI NIH HHS HL076259NHLBI NIH HHS HL089257NHLBI NIH HHS HL107920NHLBI NIH HHS P01 HL058064NHLBI NIH HHS R01 HL076259NHLBI NIH HHS R01 HL087823NHLBI NIH HHS R01 HL089257NHLBI NIH HHS R01 HL107920NHLBI NIH HHS R56 HL107920NIH HHS DP1 OD003354
6 · The paper itself

Abstract

Circulating barrier disruptive agonists bind specific cell membrane receptors and trigger signal transduction pathways leading to the activation of cell contractility and endothelial cell (EC) permeability. Although all cells in tissues including vascular EC are surrounded by compliant extracellular matrix, the impact of matrix stiffness on agonist-induced signaling, cytoskeletal remodeling and EC barrier regulation is not well understood. This study examined agonist-induced cytoskeletal and signaling changes associated with EC barrier disruption and recovery using pulmonary EC grown on compliant substrates of physiologically relevant (8.6 kPa) stiffness, very low (0.55 kPa) and very high (42 kPa) stiffness. Human pulmonary microvascular and macrovascular EC grown on 0.55 kPa substrate contained a few actin stress fibers, while stress fiber amount increased with increasing matrix stiffness. Thrombin-induced stress fiber formation was maximal in EC grown on 42 kPa substrate, diminished on 8.6 kPa substrate, and was minimal on 0.55 kPa substrate. These effects were linked to a stiffness-dependent increase in thrombin-induced phosphorylation of the Rho kinase target, myosin light chain phosphatase (MYPT1), and regulatory myosin light chains (MLC). Surprisingly, EC barrier recovery and activation of Rac GTPase-dependent barrier protective signaling reached maximal levels in EC grown on 8.6 kPa, but not on 0.55 kPa substrate. In conclusion, these data show a critical role of extracellular matrix stiffness in the regulation of the Rac/Rho signaling balance during onset and resolution of agonist-induced EC permeability. The optimal conditions for the Rho/Rac signaling switch, which provides an effective and reversible EC cytoskeletal and permeability response to agonist, are reached in cells grown on the matrix of physiologically relevant stiffness.

Indexed as

Capillary PermeabilityAcrylic ResinsCell Culture TechniquesCells, CulturedElasticityEndothelial CellsHumansHydrogelsLungMyosin-Light-Chain PhosphataseMyosin Light ChainsPhosphorylationPolyacrylamidesrac GTP-Binding Proteinsrho GTP-Binding ProteinsSignal TransductionAcrylic ResinsHydrogelsMyosin-Light-Chain PhosphataseMyosin Light ChainsPolyacrylamidesPPP1R12A protein, humanrac GTP-Binding Proteinsrho GTP-Binding ProteinsThrombin

Identifiers

PMID23296034
PMCPMC3627818
OpenAlexW2047857252

What OpenQuestion holds

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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.