Evidence map›Paper›PMID 19483084›Full record

ArticleThe Journal of biological chemistry2009

Essential role of cofilin-1 in regulating thrombin-induced RelA/p65 nuclear translocation and intercellular adhesion molecule 1 (ICAM-1) expression in endothelial cells.

Fabeha Fazal, Kaiser M Bijli, Mohd Minhajuddin, Theo Rein, Jacob N Finkelstein, Arshad Rahman

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.0field-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

41 citing papers in PubMed, 60 citations in OpenAlex.

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  17. Autophagy inhibitor 3-methyladenine protects against endothelial cell barrier dysfunction in acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2018
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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 2 institutions in 2 countries.

Fabeha FazalDepartment of Pediatrics (Neonatology), Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA. Fabeha_Fazal@urmc.rochester.edu
Kaiser M Bijli
Mohd Minhajuddin
Theo Rein
Jacob N Finkelstein
Arshad Rahman
University of Rochester · USMax Planck Institute of Psychiatry · DE

Funding

VISUAL INDICES OF NEUROTOXICITYP30ES001247 · NIEHS · UNIVERSITY OF ROCHESTER · PI Martha Susiarjo · 1985 to 2026
$42.8M
G-protein-induced Signaling of PMN-mediated Lung InjuryR01HL067424 · NHLBI · UNIVERSITY OF ROCHESTER · PI RAHMAN, ARSHAD · 2002 to 2010
$2.3M
NHLBI NIH HHS HL67424NHLBI NIH HHS R01 HL067424NIEHS NIH HHS ES-01247NIEHS NIH HHS P30 ES001247
6 · The paper itself

Abstract

Activation of RhoA/Rho-associated kinase (ROCK) pathway and the associated changes in actin cytoskeleton induced by thrombin are crucial for activation of NF-kappaB and expression of its target gene ICAM-1 in endothelial cells. However, the events acting downstream of RhoA/ROCK to mediate these responses remain unclear. Here, we show a central role of cofilin-1, an actin-binding protein that promotes actin depolymerization, in linking RhoA/ROCK pathway to dynamic alterations in actin cytoskeleton that are necessary for activation of NF-kappaB and thereby expression of ICAM-1 in these cells. Stimulation of human umbilical vein endothelial cells with thrombin resulted in Ser(3) phosphorylation/inactivation of cofilin and formation of actin stress fibers in a ROCK-dependent manner. RNA interference knockdown of cofilin-1 stabilized the actin filaments and inhibited thrombin- and RhoA-induced NF-kappaB activity. Similarly, constitutively inactive mutant of cofilin-1 (Cof1-S3D), known to stabilize the actin cytoskeleton, inhibited NF-kappaB activity by thrombin. Overexpression of wild type cofilin-1 or constitutively active cofilin-1 mutant (Cof1-S3A), known to destabilize the actin cytoskeleton, also impaired thrombin-induced NF-kappaB activity. Additionally, depletion of cofilin-1 was associated with a marked reduction in ICAM-1 expression induced by thrombin. The effect of cofilin-1 depletion on NF-kappaB activity and ICAM-1 expression occurred downstream of IkappaBalpha degradation and was a result of impaired RelA/p65 nuclear translocation and consequently, RelA/p65 binding to DNA. Together, these data show that cofilin-1 occupies a central position in RhoA-actin pathway mediating nuclear translocation of RelA/p65 and expression of ICAM-1 in endothelial cells.

Indexed as

Cell NucleusCofilin 1Endothelial CellsGene Knockdown TechniquesHumansI-kappa B ProteinsIntercellular Adhesion Molecule-1Models, BiologicalNF-KappaB Inhibitor alphaPhosphorylationPromoter Regions, GeneticProtein Kinase InhibitorsProtein Processing, Post-TranslationalProtein TransportrhoA GTP-Binding Proteinrho-Associated KinasesCofilin 1I-kappa B ProteinsIntercellular Adhesion Molecule-1NF-KappaB Inhibitor alphaNFKBIA protein, humanProtein Kinase InhibitorsrhoA GTP-Binding Proteinrho-Associated KinasesThrombinTranscription Factor RelA

Identifiers

PMID19483084
PMCPMC2742869
OpenAlexW2090595394

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.