Evidence map›Paper›PMID 27405758›Full record

ArticleThe Journal of biological chemistry2016

Transforming Growth Factor-β1 Increases DNA Methyltransferase 1 and 3a Expression through Distinct Post-transcriptional Mechanisms in Lung Fibroblasts.

Hailey B Koh, Anne M Scruggs, Steven K Huang

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.7field-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

23 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.Mammalian genome : official journal of the International Mammalian Genome Society · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Myofibroblast fate plasticity in tissue repair and fibrosis: Deactivation, apoptosis, senescence and reprogramming.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2021
    Article
  16. Influence ofCurrent issues in molecular biology · 2021
    Article
  17. Article
  18. Stomatin plays a suppressor role in non-small cell lung cancer metastasis.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2019
    Article
  19. Review
  20. Article
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

3 authors at 1 institution in 1 country.

Hailey B KohFrom the Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109.
Anne M ScruggsFrom the Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109.
Steven K HuangFrom the Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109 stehuang@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Strategic Vision & Impact on Environmental HealthP30ES017885 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Dana Dolinoy · 2011 to 2026
$21.3M
The Role of KCNMB1 and the Large Conductance Potassium (BK) Channel in Myofibroblast Differentiation and Pulmonary FibrosisR01HL127203 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HUANG, STEVEN K · 2015 to 2024
$4.4M
The Altered DNA Methylome as a Determinant of Variable Disease Progression in IPFR56HL119289 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HUANG, STEVEN K · 2014 to 2014
$436k
NHLBI NIH HHS R01 HL127203NHLBI NIH HHS R56 HL119289NIEHS NIH HHS P30 ES017885
6 · The paper itself

Abstract

DNA methylation is a fundamental epigenetic mark that plays a critical role in differentiation and is mediated by the actions of DNA methyltransferases (DNMTs). TGF-β1 is one of the most potent inducers of fibroblast differentiation, and although many of its actions on fibroblasts are well described, the ability of TGF-β1 to modulate DNA methylation in mesenchymal cells is less clear. Here, we examine the ability of TGF-β1 to modulate the expression of various DNMTs in primary lung fibroblasts (CCL210). TGF-β1 increased the protein expression, but not RNA levels, of both DNMT1 and DNMT3a. The increases in DNMT1 and DNMT3a were dependent on TGF-β1 activation of focal adhesion kinase and PI3K/Akt. Activation of mammalian target of rapamycin complex 1 by Akt resulted in increased protein translation of DNMT3a. In contrast, the increase in DNMT1 by TGF-β1 was not dependent on new protein synthesis and instead was due to decreased protein degradation. TGF-β1 treatment led to the phosphorylation and inactivation of glycogen synthase kinase-3β, which resulted in inhibition of DNMT1 ubiquitination and proteosomal degradation. The phosphorylation and inactivation of glycogen synthase kinase-3β was dependent on mammalian target of rapamycin complex 1. These results demonstrate that TGF-β1 increases expression of DNMT1 and DNMT3a through different post-transcriptional mechanisms. Because DNA methylation is critical to many processes including development and differentiation, for which TGF-β1 is known to be crucial, the ability of TGF-β1 to increase expression of both DNMT1 and DNMT3a demonstrates a novel means by which TGF-β1 may regulate DNA methylation in these cells.

Indexed as

Cell LineDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AFibroblastsGene Expression Regulation, EnzymologicGlycogen Synthase Kinase 3 betaHumansLungPhosphatidylinositol 3-KinasesProtein BiosynthesisProteolysisProto-Oncogene Proteins c-aktTransforming Growth Factor beta1DNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT1 protein, humanDNMT3A protein, humanGlycogen Synthase Kinase 3 betaGSK3B protein, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTGFB1 protein, humanTransforming Growth Factor beta1Akt PKBDNA methylationDNA methyltransferaseDNMT1DNMT3afibroblastglycogen synthase kinase 3 (GSK-3)mammalian target of rapamycin (mTOR)transforming growth factor beta (TGF-B)ubiquitylation (ubiquitination)

Identifiers

PMID27405758
PMCPMC5016670
OpenAlexW2474491659

What OpenQuestion holds

Textmetadata
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.