Evidence map›Paper›PMID 21156189›Full record

ArticleJournal of hepatology2011

Ethanol-stimulated differentiated functions of human or mouse hepatic stellate cells are mediated by connective tissue growth factor.

Li Chen, Alyssa L Charrier, Andrew Leask, Samuel W French, David R Brigstock

Abstract read
In one paragraph

Article in Journal of hepatology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

33 citing papers in PubMed, 53 citations in OpenAlex.

  1. Trial
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  5. The advance of CCN3 in fibrosis.Journal of cell communication and signaling · 2023
    Review
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  15. Pathways of production and delivery of hepatocyte exosomes.Journal of cell communication and signaling · 2018
    Article
  16. Article
  17. Review
  18. Article
  19. Article
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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

5 authors at 4 institutions in 2 countries.

Li ChenCenter for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, United States.
Alyssa L Charrier
Andrew Leask
Samuel W French
David R Brigstock
Nationwide Children's Hospital · USHarbor–UCLA Medical Center · USThe Ohio State University · USWestern University · CA

Funding

Mechanisms of CTGF-Induced Liver DiseaseR01AA016003 · NIAAA · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI BRIGSTOCK, DAVID R · 2007 to 2011
$1.7M
NIAAA NIH HHS 5R01AA016003NIAAA NIH HHS R01 AA016003
6 · The paper itself

Abstract

BACKGROUND &

aimsConnective tissue growth factor (CTGF) expression is intimately associated with hepatic fibrotic pathophysiology. In this study, CTGF production and action was investigated in ethanol-treated mouse primary hepatic stellate cells (HSC) or human LX-2 cells.

methodsCTGF, transforming growth factor-beta1 (TGF-β1), alpha-smooth muscle actin (α-SMA) or collagen α1(I) mRNA were quantified by real-time PCR after treatment of HSC with ethanol or acetaldehyde. CTGF protein production was assessed by immunoprecipitation or ELISA. Ethanol-stimulated CTGF transcription was investigated using CTGF promoter reporter constructs. The TGF-β1- or CTGF-dependency of ethanol-induced CTGF, α-SMA, or collagen α1(I) was determined using small interfering RNA (siRNA) to TGF-β1 or CTGF.

resultsIn human steatohepatitis, CTGF was produced by presumptive activated HSC. In cultured human or mouse HSC, production of CTGF, α-SMA and/or collagen was increased by ethanol treatment, an effect mimicked by acetaldehyde and blocked by 4-methylpyrazole (4-MP) or N-acetylcysteine (NAC). CTGF promoter activity was stimulated in a sustained fashion by ethanol or TGF-β1. Mutation of the Smad site or basal control element (BCE-1) in the CTGF promoter caused a 5-fold reduction in ethanol-stimulated CTGF promoter activity. Administration of TGF-β1 siRNA or CTGF siRNA significantly decreased ethanol- or acetaldehyde-stimulated mRNA or protein levels of CTGF, α-SMA or collagen I in LX-2 cells. In mouse HSC, TGF-β1- or ethanol-stimulated CTGF, α-SMA or collagen I were significantly attenuated by CTGF siRNA.

conclusionsEthanol-induced α-SMA or collagen α1(I) in HSC are mediated via TGF-β-dependent CTGF production, highlighting potential therapeutic benefits of targeting CTGF in alcoholic liver disease.

Indexed as

ActinsAnimalsBase SequenceCell LineCells, CulturedCollagen Type ICollagen Type I, alpha 1 ChainConnective Tissue Growth FactorEthanolGene ExpressionGene Knockdown TechniquesHepatic Stellate CellsHumansLiver Diseases, AlcoholicMicePromoter Regions, GeneticACTA2 protein, humanActinsalpha-smooth muscle actin, mouseCCN2 protein, humanCCN2 protein, mouseCollagen Type ICollagen Type I, alpha 1 ChainConnective Tissue Growth FactorEthanolRNA, MessengerRNA, Small InterferingSmad ProteinsTransforming Growth Factor beta1

Identifiers

PMID21156189
PMCPMC3136646
OpenAlexW2036635904

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.