Evidence map›Paper›PMID 31189969›Full record

ArticleScientific reports2019

Overexpression of miRNA-25-3p inhibits Notch1 signaling and TGF-β-induced collagen expression in hepatic stellate cells.

Berit Genz, Miranda A Coleman, Katharine M Irvine, Jamie R Kutasovic, Mariska Miranda, Francis D Gratte, Janina E E Tirnitz-Parker, John K Olynyk, Diego A Calvopina, Anna Weis and 5 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

21 citing papers in PubMed, 32 citations in OpenAlex.

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  8. Analysis of miRNAs inPharmaceuticals (Basel, Switzerland) · 2023
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  15. [Regulatory effects of microRNAs on hepatic stellate cell activation and liver fibrogenesis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2021
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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

15 authors at 6 institutions in 1 country.

Berit GenzHepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Miranda A ColemanHepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Katharine M IrvineMater Research, Translational Research Institute, Brisbane, Queensland, Australia.
Jamie R KutasovicFaculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0001-5410-3636
Mariska MirandaPersonalised Medicine Team, QIMR-Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Francis D GratteSchool of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA, Australia.
Janina E E Tirnitz-ParkerSchool of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA, Australia.
John K OlynykDepartment of Gastroenterology & Hepatology, Fiona Stanley Fremantle Hospital Group, Murdoch, Western Australia, Australia.
Diego A CalvopinaHepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Anna WeisHepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Nicole CloonanGenomic Biology Lab, QIMR-Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Harley RobinsonPrecision & Systems Biomedicine, QIMR-Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-9374-5532
Michelle M HillPrecision & Systems Biomedicine, QIMR-Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Fares Al-EjehPersonalised Medicine Team, QIMR-Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-1553-0077
Grant A RammHepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. grant.ramm@qimrberghofer.edu.au.ORCID http://orcid.org/0000-0001-7058-6201
QIMR Berghofer Medical Research Institute · AUThe University of Queensland · AUTranslational Research Institute · AUCurtin University · AUEdith Cowan University · AUMurdoch University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

During chronic liver injury hepatic stellate cells (HSCs), the principal source of extracellular matrix in the fibrotic liver, transdifferentiate into pro-fibrotic myofibroblast-like cells - a process potentially regulated by microRNAs (miRNAs). Recently, we found serum miRNA-25-3p (miR-25) levels were upregulated in children with Cystic Fibrosis (CF) without liver disease, compared to children with CF-associated liver disease and healthy individuals. Here we examine the role of miR-25 in HSC biology. MiR-25 was detected in the human HSC cell line LX-2 and in primary murine HSCs, and increased with culture-induced activation. Transient overexpression of miR-25 inhibited TGF-β and its type 1 receptor (TGFBR1) mRNA expression, TGF-β-induced Smad2 phosphorylation and subsequent collagen1α1 induction in LX-2 cells. Pull-down experiments with biotinylated miR-25 revealed Notch signaling (co-)activators ADAM-17 and FKBP14 as miR-25 targets in HSCs. NanoString analysis confirmed miR-25 regulation of Notch- and Wnt-signaling pathways. Expression of Notch signaling pathway components and endogenous Notch1 signaling was downregulated in miR-25 overexpressing LX-2 cells, as were components of Wnt signaling such as Wnt5a. We propose that miR-25 acts as a negative feedback anti-fibrotic control during HSC activation by reducing the reactivity of HSCs to TGF-β-induced collagen expression and modulating the cross-talk between Notch, Wnt and TGF-β signaling.

Indexed as

Gene Expression RegulationWnt Signaling PathwayAnimalsCell LineCollagenHepatic Stellate CellsHumansMiceMicroRNAsReceptor, Notch1Transforming Growth Factor betaCollagenMicroRNAsMIRN25 microRNA, humanMIRN25 microRNA, mouseNOTCH1 protein, humanNotch1 protein, mouseReceptor, Notch1Transforming Growth Factor beta

Identifiers

PMID31189969
PMCPMC6561916
OpenAlexW2949370569

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.