Evidence map›Paper›PMID 26208095›Full record

ArticlePloS one2015

PPARγ Ligands Attenuate Hypoxia-Induced Proliferation in Human Pulmonary Artery Smooth Muscle Cells through Modulation of MicroRNA-21.

David E Green, Tamara C Murphy, Bum-Yong Kang, Charles D Searles, C Michael Hart

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

37 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. 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

5 authors at 2 institutions in 1 country.

David E GreenDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Atlanta Veterans Affairs Medical Center / Emory University, Atlanta, GA, United States of America.
Tamara C MurphyDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Atlanta Veterans Affairs Medical Center / Emory University, Atlanta, GA, United States of America.
Bum-Yong KangDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Atlanta Veterans Affairs Medical Center / Emory University, Atlanta, GA, United States of America.
Charles D SearlesDepartment of Medicine, Division of Cardiology, Atlanta Veterans Affairs Medical Center / Emory University, Atlanta, GA, United States of America.
C Michael HartDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Atlanta Veterans Affairs Medical Center / Emory University, Atlanta, GA, United States of America.
Emory University · USVeterans Health Administration · US

Funding

PPAR gamma and Nox4 in pulmonary hypertensionR01HL102167 · NHLBI · EMORY UNIVERSITY · PI HART, C MICHAEL, SUTLIFF, ROY L · 2011 to 2018
$2.5M
MicroRNAs regulate proliferative signaling pathways in pulmonary hypertensionIK2BX001707 · VA · VETERANS HEALTH ADMINISTRATION · PI GREEN, DAVID EMERSON · 2013 to 2017
–
BLRD VA I01 BX001910BLRD VA IK2 BX001707NHLBI NIH HHS R01 HL102167
6 · The paper itself

Abstract

Pulmonary hypertension (PH) is a progressive and often fatal disorder whose pathogenesis involves pulmonary artery smooth muscle cell (PASMC) proliferation. Although modern PH therapies have significantly improved survival, continued progress rests on the discovery of novel therapies and molecular targets. MicroRNA (miR)-21 has emerged as an important non-coding RNA that contributes to PH pathogenesis by enhancing vascular cell proliferation, however little is known about available therapies that modulate its expression. We previously demonstrated that peroxisome proliferator-activated receptor gamma (PPARγ) agonists attenuated hypoxia-induced HPASMC proliferation, vascular remodeling and PH through pleiotropic actions on multiple targets, including transforming growth factor (TGF)-β1 and phosphatase and tensin homolog deleted on chromosome 10 (PTEN). PTEN is a validated target of miR-21. We therefore hypothesized that antiproliferative effects conferred by PPARγ activation are mediated through inhibition of hypoxia-induced miR-21 expression. Human PASMC monolayers were exposed to hypoxia then treated with the PPARγ agonist, rosiglitazone (RSG,10 μM), or in parallel, C57Bl/6J mice were exposed to hypoxia then treated with RSG. RSG attenuated hypoxic increases in miR-21 expression in vitro and in vivo and abrogated reductions in PTEN and PASMC proliferation. Antiproliferative effects of RSG were lost following siRNA-mediated PTEN depletion. Furthermore, miR-21 mimic decreased PTEN and stimulated PASMC proliferation, whereas miR-21 inhibition increased PTEN and attenuated hypoxia-induced HPASMC proliferation. Collectively, these results demonstrate that PPARγ ligands regulate proliferative responses to hypoxia by preventing hypoxic increases in miR-21 and reductions in PTEN. These findings further clarify molecular mechanisms that support targeting PPARγ to attenuate pathogenic derangements in PH.

Indexed as

LigandsAnimalsCell ProliferationGene ExpressionGene Expression RegulationHumansHypoxiaMaleMiceMicroRNAsMyocytes, Smooth MusclePPAR gammaPTEN PhosphohydrolasePulmonary ArteryRosiglitazoneThiazolidinedionesLigandsMicroRNAsMIRN21 microRNA, humanPPAR gammaPTEN PhosphohydrolaseRosiglitazoneThiazolidinedionesTransforming Growth Factor beta1

Identifiers

PMID26208095
PMCPMC4514882
OpenAlexW960848489

What OpenQuestion holds

Textmetadata
LicenceCC0
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.