Evidence map›Paper›PMID 25665524›Full record

ArticleNature communications2015

Pharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation.

Ping-Xia Zhang, Jijun Cheng, Siying Zou, Anthony D D'Souza, Jonathan L Koff, Jun Lu, Patty J Lee, Diane S Krause, Marie E Egan, Emanuela M Bruscia

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
9.6field-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

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
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  12. Article
  13. Microvesicle-Derived miRNAs Regulate Proinflammatory Macrophage Activation in the Lung Following Ozone Exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2022
    Article
  14. Article
  15. Review
  16. TheInternational journal of molecular sciences · 2021
    Article
  17. Article
  18. Article
  19. Review
  20. The Multifaceted Roles of MicroRNAs in Cystic Fibrosis.Diagnostics (Basel, Switzerland) · 2020
    Review

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

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

10 authors at 1 institution in 1 country.

Ping-Xia Zhang1] Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA [2] Department of Laboratory Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Jijun Cheng1] Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA [2] Yale Stem Cell Center, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA [3] Yale Cancer Center, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Siying ZouDepartment of Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Anthony D D'SouzaDepartment of Laboratory Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Jonathan L KoffDepartment of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Jun Lu1] Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA [2] Yale Stem Cell Center, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA [3] Yale Cancer Center, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Patty J LeeDepartment of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Diane S Krause1] Department of Laboratory Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA [2] Yale Stem Cell Center, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA [3] Yale Cancer Center, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA [4] Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Marie E Egan1] Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA [2] Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Emanuela M BrusciaDepartment of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Yale University · US

Funding

CFTR and the Immune ResponseR01HL093004 · NHLBI · YALE UNIVERSITY · PI BRUSCIA, EMANUELA MARINA, EGAN, MARIE E · 2010 to 2014
$2.0M
NHLBI NIH HHS R01 HL093004
6 · The paper itself

Abstract

In cystic fibrosis (CF) patients, hyper-inflammation is a key factor in lung destruction and disease morbidity. We have previously demonstrated that macrophages drive the lung hyper-inflammatory response to LPS in CF mice, because of reduced levels of the scaffold protein CAV1 with subsequent uncontrolled TLR4 signalling. Here we show that reduced CAV1 and, consequently, increased TLR4 signalling, in human and murine CF macrophages and murine CF lungs, is caused by high microRNA-199a-5p levels, which are PI3K/AKT-dependent. Downregulation of microRNA-199a-5p or increased AKT signalling restores CAV1 expression and reduces hyper-inflammation in CF macrophages. Importantly, the FDA-approved drug celecoxib re-establishes the AKT/miR-199a-5p/CAV1 axis in CF macrophages, and ameliorates lung hyper-inflammation in Cftr-deficient mice. Thus, we identify the AKT/miR-199a-5p/CAV1 pathway as a regulator of innate immunity, which is dysfunctional in CF macrophages contributing to lung hyper-inflammation. In addition, we found that this pathway can be targeted by celecoxib.

Indexed as

AnimalsCaveolin 1CelecoxibCystic FibrosisHumansInflammationLungMacrophagesMice, Inbred C57BLMicroRNAsModels, BiologicalPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionToll-Like Receptor 4Caveolin 1CelecoxibMicroRNAsmirn199 microRNA, humanMirn199 microRNA, mousePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktToll-Like Receptor 4

Identifiers

PMID25665524
PMCPMC4324503
OpenAlexW2044735278

What OpenQuestion holds

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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.