Evidence map›Paper›PMID 24585879›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2014

The RhoA guanine nucleotide exchange factor, LARG, mediates ICAM-1-dependent mechanotransduction in endothelial cells to stimulate transendothelial migration.

Elizabeth C Lessey-Morillon, Lukas D Osborne, Elizabeth Monaghan-Benson, Christophe Guilluy, E Timothy O'Brien, Richard Superfine, Keith Burridge

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

42 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
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  14. ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor-induced leak.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  15. Viscoelasticity, Like Forces, Plays a Role in Mechanotransduction.Frontiers in cell and developmental biology · 2022
    Review
  16. Transcriptomic and functional studies reveal undermined chemotactic and angiostimulatory properties of aged microglia during stroke recovery.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020
    Article
  17. Review
  18. Review
  19. Article
  20. Mechanotransduction: from the cell surface to the nucleus via RhoA.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019
    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

7 authors at 1 institution in 1 country.

Elizabeth C Lessey-MorillonDepartment of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
Lukas D Osborne
Elizabeth Monaghan-Benson
Christophe Guilluy
E Timothy O'Brien
Richard Superfine
Keith Burridge
University of North Carolina at Chapel Hill · US

Funding

INTERACTIVE GRAPHICS FOR MOLECULAR STUDIES &MICROSCOPYP41EB002025 · NIBIB · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SUPERFINE, RICHARD · 2003 to 2019
$16.9M
Pre-doctoral Training Program in Integrative Vascular BiologyT32HL069768 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Christopher P. Mack · 2002 to 2026
$9.7M
STRUCTURE/FUNCTION OF FOCAL ADHESIONSR01GM029860 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BURRIDGE, KEITH · 1985 to 2018
$6.7M
The Platelet-Leukocyte Switch in Vascular DiseaseP01HL080166 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JACOBSON, KENNETH A · 2006 to 2010
$6.7M
Rho-mediated Signaling in Lung Endothelial Cells Induced by Neutrophil AdhesionR01HL114388 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BURRIDGE, KEITH, DOERSCHUK, CLAIRE M · 2012 to 2016
$3.0M
NHLBI NIH HHS HL080166NHLBI NIH HHS HL114388NHLBI NIH HHS P01 HL080166NHLBI NIH HHS R01 HL114388NHLBI NIH HHS T32 HL069768NHLBI NIH HHS TL32HL069768NIBIB NIH HHS P41 EB002025NIBIB NIH HHS P41-EB002025-23A1NIGMS NIH HHS GM029860NIGMS NIH HHS R01 GM029860
6 · The paper itself

Abstract

RhoA-mediated cytoskeletal rearrangements in endothelial cells (ECs) play an active role in leukocyte transendothelial cell migration (TEM), a normal physiological process in which leukocytes cross the endothelium to enter the underlying tissue. Although much has been learned about RhoA signaling pathways downstream from ICAM-1 in ECs, little is known about the consequences of the tractional forces that leukocytes generate on ECs as they migrate over the surface before TEM. We have found that after applying mechanical forces to ICAM-1 clusters, there is an increase in cellular stiffening and enhanced RhoA signaling compared with ICAM-1 clustering alone. We have identified that leukemia-associated Rho guanine nucleotide exchange factor (LARG), also known as Rho GEF 12 (ARHGEF12) acts downstream of clustered ICAM-1 to increase RhoA activity, and that this pathway is further enhanced by mechanical force on ICAM-1. Depletion of LARG decreases leukocyte crawling and inhibits TEM. To our knowledge, this is the first report of endothelial LARG regulating leukocyte behavior and EC stiffening in response to tractional forces generated by leukocytes.

Indexed as

Blotting, WesternCells, CulturedCytochalasin DCytoskeletonEndothelial CellsHumansHuman Umbilical Vein Endothelial CellsInfant, NewbornIntercellular Adhesion Molecule-1Mechanotransduction, CellularMicroscopy, FluorescenceNucleic Acid Synthesis InhibitorsRho Guanine Nucleotide Exchange FactorsRNA InterferenceSignal TransductionStress, MechanicalARHGEF12 protein, humanCytochalasin DIntercellular Adhesion Molecule-1Nucleic Acid Synthesis InhibitorsRho Guanine Nucleotide Exchange Factors

Identifiers

PMID24585879
PMCPMC3991232
OpenAlexW1953931070

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.