Evidence map›Paper›PMID 22278637›Full record

ArticleHepatology (Baltimore, Md.)2012

Inhibitory effects of microRNA 19b in hepatic stellate cell-mediated fibrogenesis.

Ashley M Lakner, Nury M Steuerwald, Tracy L Walling, Sriparna Ghosh, Ting Li, Iain H McKillop, Mark W Russo, Herbert L Bonkovsky, Laura W Schrum

Open access · greenAbstract readComparative Study
In one paragraph

Article in Hepatology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 1 pooled it
11.9field-weighted citation impact, top 1% 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

98 citing papers in PubMed, 1 synthesis or guideline pooled it, 201 citations in OpenAlex.

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38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Ashley M LaknerDepartment of Biology, University of North Carolina at Charlotte, Charlotte, NC 28203, USA.
Nury M Steuerwald
Tracy L Walling
Sriparna Ghosh
Ting Li
Iain H McKillop
Mark W Russo
Herbert L Bonkovsky
Laura W Schrum
Carolinas Medical Center · USUniversity of North Carolina at Charlotte · USUConn Health · US

Funding

NFkB-mediated collagen regulation by SAMe in HSCsR01AA014891 · NIAAA · UNIVERSITY OF NORTH CAROLINA CHARLOTTE · PI SCHRUM, LAURA W · 2005 to 2008
$838k
NIAAA NIH HHS R01 AA014891NIAAA NIH HHS R01AA014891
6 · The paper itself

Abstract

unlabelledHepatic stellate cell (HSC) activation is a pivotal event in initiation and progression of hepatic fibrosis and a major contributor to collagen deposition driven by transforming growth factor beta (TGF-β). MicroRNAs (miRs), small noncoding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key regulatory molecules in chronic liver disease. We investigated differentially expressed miRs in quiescent and activated HSCs to identify novel regulators of profibrotic TGF-β signaling. miR microarray analysis was performed on quiescent and activated rat HSCs. Members of the miR-17-92 cluster (19a, 19b, 92a) were significantly down-regulated in activated HSCs. Because miR 19b showed the highest fold-change of the cluster members, activated HSCs were transfected with miR 19b mimic or negative control and TGF-β signaling and HSC activation assessed. miR 19b expression was determined in fibrotic rat and human liver specimens. miR 19b mimic negatively regulated TGF-β signaling components demonstrated by decreased TGF-β receptor II (TGF-βRII) and SMAD3 expression. Computational prediction of miR 19b binding to the 3' untranslated region of TGF-βRII was validated by luciferase reporter assay. Inhibition of TGF-β signaling by miR 19b was confirmed by decreased expression of type I collagen and by blocking TGF-β-induced expression of α1(I) and α2(I) procollagen mRNAs. miR 19b blunted the activated HSC phenotype by morphological assessment and decreased smooth muscle α-actin expression. Additionally, miR 19b expression was markedly diminished in fibrotic rat liver compared with normal liver; similarly, miR 19b expression was markedly down-regulated in fibrotic compared with normal human livers.

conclusionmiR 19b is a novel regulator of TGF-β signaling in HSCs, suggesting a potential therapeutic approach for hepatic fibrosis.

Indexed as

AnimalsCells, CulturedDisease Models, AnimalDown-RegulationGene Expression RegulationHepatic Stellate CellsHumansImmunohistochemistryLiver CirrhosisMaleMicroRNAsRandom AllocationRatsRats, Sprague-DawleyReal-Time Polymerase Chain ReactionSensitivity and SpecificityMicroRNAsTrans-ActivatorsTransforming Growth Factor beta

Identifiers

PMID22278637
PMCPMC3342471
OpenAlexW2095297471

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.