Evidence map›Paper›PMID 24762191›Full record

ArticleRespiratory research2014

Arsenic trioxide inhibits transforming growth factor-β1-induced fibroblast to myofibroblast differentiation in vitro and bleomycin induced lung fibrosis in vivo.

Fayong Luo, Yan Zhuang, Mark D Sides, Cecilia G Sanchez, Bin Shan, Eric S White, Joseph A Lasky

Abstract read
In one paragraph

Article in Respiratory research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
–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

37 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  9. Review
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  11. Oral arsenite exposure induces inflammation and apoptosis in pulmonary tissue: acute and chronic evaluation in young and adult mice.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024
    Article
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  17. Paradoxical effects of arsenic in the lungs.Environmental health and preventive medicine · 2021
    Review
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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

7 authors.

Fayong Luo
Yan Zhuang
Mark D Sides
Cecilia G Sanchez
Bin Shan
Eric S White
Joseph A LaskyDepartment of Medicine, Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Tulane University Health Science Center, New Orleans, LA 70112, USA. jlasky@tulane.edu.

Funding

The role of the CMV-associated reactive oxygen species in age-relatedP20GM103629 · NIGMS · TULANE UNIVERSITY OF LOUISIANA · PI JAZWINSKI, S MICHAL · 2012 to 2021
$22.4M
Matrix and Bioreactors for Human Lung RegenerationU01HL111016 · NHLBI · YALE UNIVERSITY · PI NIKLASON, LAURA E, WHITE, ERIC S · 2012 to 2016
$3.2M
Role of EIIIA fibronectin in pulmonary fibrosisR01HL085083 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WHITE, ERIC S · 2007 to 2011
$1.9M
NHLBI NIH HHS R01 HL085083NHLBI NIH HHS U01 HL111016NIGMS NIH HHS P20 GM103629
6 · The paper itself

Abstract

backgroundIdiopathic pulmonary fibrosis (IPF) is a progressive disease of insidious onset, and is responsible for up to 30,000 deaths per year in the U.S. Excessive production of extracellular matrix by myofibroblasts has been shown to be an important pathological feature in IPF. TGF-β1 is expressed in fibrotic lung and promotes fibroblast to myofibroblast differentiation (FMD) as well as matrix deposition.

methodsTo identify the mechanism of Arsenic trioxide's (ATO)'s anti-fibrotic effect in vitro, normal human lung fibroblasts (NHLFs) were treated with ATO for 24 hours and were then exposed to TGF-β1 (1 ng/ml) before harvesting at multiple time points. To investigate whether ATO is able to alleviate lung fibrosis in vivo, C57BL/6 mice were administered bleomycin by oropharyngeal aspiration and ATO was injected intraperitoneally daily for 14 days. Quantitative real-time PCR, western blotting, and immunofluorescent staining were used to assess the expression of fibrotic markers such as α-smooth muscle actin (α-SMA) and α-1 type I collagen.

resultsTreatment of NHLFs with ATO at very low concentrations (10-20nM) inhibits TGF-β1-induced α-smooth muscle actin (α-SMA) and α-1 type I collagen mRNA and protein expression. ATO also diminishes the TGF-β1-mediated contractile response in NHLFs. ATO's down-regulation of profibrotic molecules is associated with inhibition of Akt, as well as Smad2/Smad3 phosphorylation. TGF-β1-induced H2O2 and NOX-4 mRNA expression are also blocked by ATO. ATO-mediated reduction in Smad3 phosphorylation correlated with a reduction of promyelocytic leukemia (PML) nuclear bodies and PML protein expression. PML-/- mouse embryonic fibroblasts (MEFs) showed decreased fibronectin and PAI-1 expression in response to TGF-β1. Daily intraperitoneal injection of ATO (1 mg/kg) in C57BL/6 mice inhibits bleomycin induced lung α-1 type I collagen mRNA and protein expression.

conclusionsIn summary, these data indicate that low concentrations of ATO inhibit TGF-β1-induced fibroblast to myofibroblast differentiation and decreases bleomycin induced pulmonary fibrosis.

Indexed as

AnimalsArsenicalsArsenic TrioxideBleomycinCells, CulturedCell TransdifferentiationFibroblastsHumansLungMiceMice, Inbred C57BLMyofibroblastsOxidesPulmonary FibrosisTransforming Growth Factor beta1ArsenicalsArsenic TrioxideBleomycinOxidesTransforming Growth Factor beta1

Identifiers

PMID24762191
PMCPMC4113202

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.