Evidence map›Paper›PMID 24926665›Full record

ArticlePloS one2014

RNA-Seq transcriptome profiling identifies CRISPLD2 as a glucocorticoid responsive gene that modulates cytokine function in airway smooth muscle cells.

Blanca E Himes, Xiaofeng Jiang, Peter Wagner, Ruoxi Hu, Qiyu Wang, Barbara Klanderman, Reid M Whitaker, Qingling Duan, Jessica Lasky-Su, Christina Nikolos and 6 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 1 pooled it
8.0field-weighted citation impact, top 2% 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

92 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.

  1. Pooled it
  2. International journal of molecular sciences · 2026
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  3. Efficient and Tidy Manipulation of Annotated Matrix Data with plyxp.bioRxiv : the preprint server for biology · 2026
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  4. Review
  5. Frequent exacerbator-a novel endotype of pediatric asthma.The Journal of allergy and clinical immunology · 2025
    Review
  6. Review
  7. Pharmacogenetics of childhood uncontrolled asthma.Expert review of clinical immunology · 2025
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
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  20. Article

32 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

16 authors at 5 institutions in 1 country.

Blanca E HimesChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Partners HealthCare Personalized Medicine, Boston, Massachusetts, United States of America; Children's Hospital Informatics Program, Boston, Massachusetts, United States of America.
Xiaofeng JiangProgram in Molecular and Integrative Physiological Sciences, Departments of Environmental Health, and Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
Peter WagnerProgram in Molecular and Integrative Physiological Sciences, Departments of Environmental Health, and Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
Ruoxi HuProgram in Molecular and Integrative Physiological Sciences, Departments of Environmental Health, and Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
Qiyu WangProgram in Molecular and Integrative Physiological Sciences, Departments of Environmental Health, and Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
Barbara KlandermanPartners HealthCare Personalized Medicine, Boston, Massachusetts, United States of America.
Reid M WhitakerChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Qingling DuanChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Jessica Lasky-SuChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Christina NikolosPulmonary, Allergy and Critical Care Division, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
William JesterPulmonary, Allergy and Critical Care Division, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Martin JohnsonPulmonary, Allergy and Critical Care Division, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Reynold A PanettieriPulmonary, Allergy and Critical Care Division, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Kelan G TantisiraChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Scott T WeissChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Partners HealthCare Personalized Medicine, Boston, Massachusetts, United States of America.
Quan LuProgram in Molecular and Integrative Physiological Sciences, Departments of Environmental Health, and Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
Harvard University · USUniversity of Pennsylvania · USBoston Children's Hospital · USBrigham and Women's Hospital · USMass General Brigham · US

Funding

THE PHARMACOGENETICS OF ASTHMA TREATMENTU01HL065899 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI TANTISIRA, KELAN G, WEISS, SCOTT T · 2000 to 2014
$38.5M
Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Trevor M Penning · 2006 to 2026
$35.3M
Project 4 - OGR1- and TSPO- dependent mechanisms mediated by benzodiazepines affecting ASM contractionP01HL114471 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI PANETTIERI, REYNOLD ALEXANDER · 2013 to 2023
$23.9M
Training Program in Molecular and Integrative Physiological SciencesT32HL007118 · NHLBI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI LU, QUAN · 1985 to 2025
$14.3M
RGS: A Molecular Switch Regulating Irreversible ASM Growth/Contraction in AsthmaR01HL097796 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI PANETTIERI, REYNOLD ALEXANDER · 2009 to 2012
$2.1M
Mechanism and Function of Beta-2 Adrenergic Receptor Degradation in the LungR01HL114769 · NHLBI · HARVARD SCHOOL OF PUBLIC HEALTH · PI LU, QUAN · 2013 to 2016
$1.6M
INTEGRATIVE GENOMICS APPROACHES TO MODEL THE GENETIC ARCHITECTURE OF ASTHMAR00HL105663 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI HIMES, BLANCA E · 2013 to 2015
$702k
INTEGRATIVE GENOMICS APPROACHES TO MODEL THE GENETIC ARCHITECTURE OF ASTHMAK99HL105663 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI HIMES, BLANCA E · 2011 to 2012
$275k
NHLBI NIH HHS K99 HL105663NHLBI NIH HHS P01 HL114471NHLBI NIH HHS R00 HL105663NHLBI NIH HHS R01 HL097796NHLBI NIH HHS R01 HL114769NHLBI NIH HHS T32 HL007118NHLBI NIH HHS U01 HL065899NHLBI NIH HHS U01 HL65899NIEHS NIH HHS P30 ES013508
6 · The paper itself

Abstract

Asthma is a chronic inflammatory respiratory disease that affects over 300 million people worldwide. Glucocorticoids are a mainstay therapy for asthma because they exert anti-inflammatory effects in multiple lung tissues, including the airway smooth muscle (ASM). However, the mechanism by which glucocorticoids suppress inflammation in ASM remains poorly understood. Using RNA-Seq, a high-throughput sequencing method, we characterized transcriptomic changes in four primary human ASM cell lines that were treated with dexamethasone--a potent synthetic glucocorticoid (1 µM for 18 hours). Based on a Benjamini-Hochberg corrected p-value <0.05, we identified 316 differentially expressed genes, including both well known (DUSP1, KLF15, PER1, TSC22D3) and less investigated (C7, CCDC69, CRISPLD2) glucocorticoid-responsive genes. CRISPLD2, which encodes a secreted protein previously implicated in lung development and endotoxin regulation, was found to have SNPs that were moderately associated with inhaled corticosteroid resistance and bronchodilator response among asthma patients in two previously conducted genome-wide association studies. Quantitative RT-PCR and Western blotting showed that dexamethasone treatment significantly increased CRISPLD2 mRNA and protein expression in ASM cells. CRISPLD2 expression was also induced by the inflammatory cytokine IL1β, and small interfering RNA-mediated knockdown of CRISPLD2 further increased IL1β-induced expression of IL6 and IL8. Our findings offer a comprehensive view of the effect of a glucocorticoid on the ASM transcriptome and identify CRISPLD2 as an asthma pharmacogenetics candidate gene that regulates anti-inflammatory effects of glucocorticoids in the ASM.

Indexed as

Administration, InhalationAnti-Inflammatory AgentsAsthmaCell Adhesion MoleculesCell LineDexamethasoneGene Expression ProfilingGene Expression RegulationHumansInterferon Regulatory FactorsLungMuscle, SmoothPolymorphism, Single NucleotideSequence Analysis, RNAAnti-Inflammatory AgentsCell Adhesion MoleculesCRISPLD2 protein, humanDexamethasoneInterferon Regulatory Factors

Identifiers

PMID24926665
PMCPMC4057123
OpenAlexW2100596675

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.