Evidence map›Paper›PMID 28910321›Full record

ArticlePloS one2017

Identification of transforming growth factor-beta-regulated microRNAs and the microRNA-targetomes in primary lung fibroblasts.

Jennie Ong, Wim Timens, Vijay Rajendran, Arjan Algra, Avrum Spira, Marc E Lenburg, Joshua D Campbell, Maarten van den Berge, Dirkje S Postma, Anke van den Berg and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

20 citing papers in PubMed, 41 citations in OpenAlex.

  1. Exploring the Roles of Wnt Signaling Pathway and Non-Coding RNAs in COPD.International journal of chronic obstructive pulmonary disease · 2026
    Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Nerve Growth Factor: A Potential Therapeutic Target for Lung Diseases.International journal of molecular sciences · 2021
    Review
  11. Review
  12. Homeobox protein Hhex negatively regulates Treg cells by inhibiting Foxp3 expression and function.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  13. Article
  14. Article
  15. Pleiotropic microRNA-21 in pulmonary remodeling: novel insights for molecular mechanism and present advancements.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2019
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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

12 authors at 2 institutions in 2 countries.

Jennie OngUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.ORCID http://orcid.org/0000-0002-9819-7870
Wim TimensUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.
Vijay RajendranUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.
Arjan AlgraUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.
Avrum SpiraBoston University, School of Medicine, Department of Medicine, Section of Computational Biomedicine, Boston, Massachusetts, United States of America.
Marc E LenburgBoston University, School of Medicine, Department of Medicine, Section of Computational Biomedicine, Boston, Massachusetts, United States of America.
Joshua D CampbellBoston University, School of Medicine, Department of Medicine, Section of Computational Biomedicine, Boston, Massachusetts, United States of America.
Maarten van den BergeUniversity of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.
Dirkje S PostmaUniversity of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.
Anke van den BergUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.
Joost KluiverUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.
Corry-Anke BrandsmaUniversity of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.
University Medical Center Groningen · NLBoston University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLung fibroblasts are involved in extracellular matrix homeostasis, which is mainly regulated by transforming growth factor-beta (TGF-β), and are therefore crucial in lung tissue repair and remodeling. Abnormal repair and remodeling has been observed in lung diseases like COPD. As miRNA levels can be influenced by TGF-β, we hypothesized that TGF-β influences miRNA expression in lung fibroblasts, thereby affecting their function. MATERIALS AND

methodsWe investigated TGF-β1-induced miRNA expression changes in 9 control primary parenchymal lung fibroblasts using miRNA arrays. TGF-β1-induced miRNA expression changes were validated and replicated in an independent set of lung fibroblasts composted of 10 controls and 15 COPD patients using qRT-PCR. Ago2-immunoprecipitation followed by mRNA expression profiling was used to identify the miRNA-targetomes of unstimulated and TGF-β1-stimulated primary lung fibroblasts (n = 2). The genes affected by TGF-β1-modulated miRNAs were identified by comparing the miRNA targetomes of unstimulated and TGF-β1-stimulated fibroblasts.

resultsTwenty-nine miRNAs were significantly differentially expressed after TGF-β1 stimulation (FDR<0.05). The TGF-β1-induced miR-455-3p and miR-21-3p expression changes were validated and replicated, with in addition, lower miR-455-3p levels in COPD (p<0.05). We identified 964 and 945 genes in the miRNA-targetomes of unstimulated and TGF-β1-stimulated lung fibroblasts, respectively. The TGF-β and Wnt pathways were significantly enriched among the Ago2-IP enriched and predicted targets of miR-455-3p and miR-21-3p. The miR-455-3p target genes HN1, NGF, STRADB, DLD and ANO3 and the miR-21-3p target genes HHEX, CHORDC1 and ZBTB49 were consistently more enriched after TGF-β1 stimulation.

conclusionTwo miRNAs, miR-455-3p and miR-21-3p, were induced by TGF-β1 in lung fibroblasts. The significant Ago2-IP enrichment of targets of these miRNAs related to the TGF-β and/or Wnt pathways (NGF, DLD, HHEX) in TGF-β1-stimulated fibroblasts suggest a role for these miRNAs in lung diseases by affecting lung fibroblast function.

Indexed as

AgedArgonaute ProteinsCells, CulturedFemaleFibroblastsGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksHumansLungMaleMicroRNAsMiddle AgedOligonucleotide Array Sequence AnalysisPulmonary Disease, Chronic ObstructiveTransforming Growth Factor betaAGO2 protein, humanArgonaute ProteinsMicroRNAsTransforming Growth Factor beta

Identifiers

PMID28910321
PMCPMC5599028
OpenAlexW2754640436

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.