Evidence map›Paper›PMID 22393274›Full record

ArticleMolecular vision2012

Halofuginone down-regulates Smad3 expression and inhibits the TGFbeta-induced expression of fibrotic markers in human corneal fibroblasts.

Elizabeth F Nelson, Craig W Huang, Jillian M Ewel, Angela A Chang, Ching Yuan

Open access · greenAbstract read
In one paragraph

Article in Molecular vision, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
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  8. Antifibrotic therapy to normalize the tumor microenvironment.Journal of translational medicine · 2020
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  20. Halofuginone - the multifaceted molecule.Molecules (Basel, Switzerland) · 2015
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Elizabeth F NelsonDepartment of Ophthalmology, University of Minnesota, Minneapolis, MN 55455, USA.
Craig W Huang
Jillian M Ewel
Angela A Chang
Ching Yuan
University of Minnesota · US

Funding

Visual TestingP30EY011374 · NEI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI NEWMAN, ERIC A · 1996 to 2019
$8.8M
Smad3 inhibitors for ophthalmic applicationsR21EY019552 · NEI · UNIVERSITY OF MINNESOTA · PI YUAN, CHING · 2009 to 2010
$415k
Treatment of BIGH3-related Corneal Dystrophies with MeptidesR21EY017852 · NEI · UNIVERSITY OF MINNESOTA · PI YUAN, CHING · 2007 to 2008
$370k
NEI NIH HHS EY017852NEI NIH HHS EY019552NEI NIH HHS P30 EY011374NEI NIH HHS R21 EY017852NEI NIH HHS R21 EY019552
6 · The paper itself

Abstract

purposeDue to its ability to disrupt transforming growth factor beta (TGF-β) signaling, halofuginone has been successfully used to treat various fibrotic disorders. Here we investigated the antifibrotic potential of halofuginone in human corneal fibroblasts.

methodsHuman corneal fibroblasts were isolated from human donor corneas for in vitro experiments. TGF-β was used to stimulate pro-fibrotic responses from corneal fibroblasts under halofuginone treatment. The expression of alpha smooth muscle actin (α-SMA) and fibronectin was analyzed by western blots. Phalloidin toxin was used to stain cultures for stress fiber assemblies. Quantitative reverse transcription PCR (qRT-PCR) and immunostaining were used to analyze the expression of type I collagen mRNA and protein, respectively. The expression of Smad2, Smad3, phospho-Smad2, and phospho-Smad3 was determined by western blots.

resultsHalofuginone was well tolerated by human corneal fibroblasts up to 10 ng/ml as demonstrated by a cell viability assay. At this concentration, TGF-β-induced expression of the fibrotic markers α-SMA, fibronectin, and type I collagen was significantly reduced. Interestingly, under our experimental conditions, halofuginone treatment led to reduced protein expression of Smad3, which was both dose- and time-dependent.

conclusionsOur results suggest that halofuginone may exert its antifibrotic effects in the cornea via a novel molecular mechanism and may be used as an antifibrotic agent for corneal fibrosis treatment.

Indexed as

ActinsBiomarkersCells, CulturedCell SurvivalCollagen Type ICorneaDose-Response Relationship, DrugFibroblastsFibronectinsFibrosisGene Expression RegulationHumansPiperidinesProtein Synthesis InhibitorsQuinazolinonesSignal TransductionActinsBiomarkersCollagen Type IFibronectinshalofuginonePiperidinesProtein Synthesis InhibitorsQuinazolinonesSmad3 ProteinSMAD3 protein, humanTransforming Growth Factor beta1

Identifiers

PMID22393274
PMCPMC3291522
OpenAlexW2096522371

What OpenQuestion holds

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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.