Evidence map›Paper›PMID 27444019›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Hhip haploinsufficiency sensitizes mice to age-related emphysema.

Taotao Lao, Zhiqiang Jiang, Jeong Yun, Weiliang Qiu, Feng Guo, Chunfang Huang, John Dominic Mancini, Kushagra Gupta, Maria E Laucho-Contreras, Zun Zar Chi Naing and 5 more

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
6.9field-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

49 citing papers in PubMed, 71 citations in OpenAlex.

  1. Trial
  2. Preclinical models of COPD: a state of the art review.The European respiratory journal · 2026
    Review
  3. HHIP's dynamic role in epithelial wound healing reveals a potential mechanism of COPD susceptibility.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
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  12. Breathing new life into the study of COPD with genes identified from genome-wide association studies.European respiratory review : an official journal of the European Respiratory Society · 2024
    Review
  13. Article
  14. Activation of CD8American journal of respiratory and critical care medicine · 2023
    Article
  15. Review
  16. AKT Phosphorylates FAM13A and Promotes Its Degradation via CUL4A/DDB1/DCAF1 E3 Complex.American journal of respiratory cell and molecular biology · 2023
    Article
  17. Article
  18. Article
  19. Hedgehog-interacting protein acts in the habenula to regulate nicotine intake.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  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

15 authors at 2 institutions in 1 country.

Taotao LaoChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
Zhiqiang JiangChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
Jeong YunChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
Weiliang QiuChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
Feng GuoChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
Chunfang HuangChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
John Dominic ManciniChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
Kushagra GuptaDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
Maria E Laucho-ContrerasDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Chronic Obstructive Pulmonary Disease Program, The Lovelace Respiratory Research Institute, Albuquerque, NM 87108;
Zun Zar Chi NaingChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
Li ZhangDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
Mark A PerrellaDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Pediatric Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.
Caroline A OwenDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Chronic Obstructive Pulmonary Disease Program, The Lovelace Respiratory Research Institute, Albuquerque, NM 87108;
Edwin K SilvermanChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
Xiaobo ZhouChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; xiaobo.zhou@channing.harvard.edu.
Brigham and Women's Hospital · USHarvard University · US

Funding

Respiratory Computational Discovery CoreP01HL114501 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHOI, MARY E · 2013 to 2025
$24.9M
Systems Biology, Bioinformatics, and BiostatisticsP01HL105339 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2011 to 2015
$12.2M
Fine Mapping of COPD Susceptibility GenesR01HL075478 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2004 to 2012
$6.4M
Metabolic Control of Stemness in lung epithelial progenitors by FAM13AR01HL127200 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI ZHOU, ANNY XIAOBO · 2015 to 2024
$4.9M
Targeting MMP9 to Improve Outcomes in Serious Influenza InfectionsR01AI111475 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI HARROD, KEVIN S, LEVY, BRUCE D · 2014 to 2018
$4.3M
Using Networks to Assign Gene Function in Lung DiseaseR01HL111759 · NHLBI · DANA-FARBER CANCER INST · PI QUACKENBUSH, JOHN, SILVERMAN, EDWIN K · 2012 to 2015
$3.4M
Functional Genomic Approaches to Dissect COPD GWAS LociR33HL120794 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K, ZHOU, ANNY XIAOBO · 2016 to 2018
$1.7M
Novel Anti-inflammatory Activities For ADAM8 In Pulmonary EmphysemaR21HL111835 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI OWEN, CAROLINE A · 2012 to 2013
$456k
NHLBI NIH HHS P01 HL105339NHLBI NIH HHS P01 HL114501NHLBI NIH HHS R01 HL075478NHLBI NIH HHS R01 HL111759NHLBI NIH HHS R01 HL127200NHLBI NIH HHS R21 HL111835NHLBI NIH HHS R33 HL120794NIAID NIH HHS R01 AI111475
6 · The paper itself

Abstract

Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip(+/-)), we observed increased lung compliance and spontaneous emphysema in Hhip(+/-) mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip(+/-) vs. Hhip(+/+) mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip(+/-) mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip(+/-) mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip(+/-) mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip.

Indexed as

HaploinsufficiencyAcetylcysteineAge FactorsAnimalsCarrier ProteinsEmphysemaGlutathioneGlutathione S-Transferase piLungLung ComplianceMembrane GlycoproteinsMiceMice, Inbred C57BLOxidative StressAcetylcysteineCarrier ProteinsGlutathioneGlutathione S-Transferase piGstp1 protein, mouseHhip protein, mouseMembrane GlycoproteinsagingCOPDemphysemaHHIPoxidative stress

Identifiers

PMID27444019
PMCPMC4987811
OpenAlexW2507089055

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.