Evidence map›Paper›PMID 27842563›Full record

ArticleJournal of hematology & oncology2016

Novel extracellular and nuclear caspase-1 and inflammasomes propagate inflammation and regulate gene expression: a comprehensive database mining study.

Luqiao Wang, Hangfei Fu, Gayani Nanayakkara, Yafeng Li, Ying Shao, Candice Johnson, Jiali Cheng, William Y Yang, Fan Yang, Muriel Lavallee and 8 more

Open access · goldAbstract read
In one paragraph

Article in Journal of hematology & oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 5% 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

71 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Caspase-1 in cancer and inflammatory diseases: a potential therapeutic target.Apoptosis : an international journal on programmed cell death · 2026
    Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Canonical and non-canonical functions of NLRP3.Journal of advanced research · 2023
    Review
  12. Article
  13. Review
  14. The Effect of Extracellular Vesicles on Thrombosis.Journal of cardiovascular translational research · 2023
    Review
  15. Article
  16. Cigarette Smoke Modulates Inflammation and ImmunityAntioxidants & redox signaling · 2023
    Review
  17. Review
  18. Article
  19. Article
  20. Article

11 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

18 authors at 3 institutions in 2 countries.

Luqiao WangCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Hangfei FuCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Gayani NanayakkaraCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Yafeng LiCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Ying ShaoCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Candice JohnsonCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Jiali ChengCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
William Y YangCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Fan YangCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Muriel LavalleeCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Yanjie XuCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Xiaoshu ChengDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, Jiangxi, 330006, China.
Hang XiCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Jonathan YiCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Jun YuCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Eric T ChoiCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Hong WangCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.
Xiaofeng YangCenters for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA. xfyang@temple.edu.
Temple University · USNanchang University · CNPhiladelphia University · US

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Margaret von Mehren · 1985 to 2026
$138.8M
Caspase-1 activation mediates chronic kidney disease-accelerated atherosclerosisR01HL131460 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI CHOI, ERIC T., WANG, HONG · 2016 to 2019
$2.8M
IL-35 suppression of endothelial cell activation and atherosclerosisR01HL132399 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI YANG, XIAOFENG · 2017 to 2020
$2.3M
ER-associated protein Reticulon in atherosclerosisR01HL126933 · NHLBI · YALE UNIVERSITY · PI YU, JUN · 2015 to 2018
$1.6M
NCI NIH HHS P30 CA006927NHLBI NIH HHS R01 HL126933NHLBI NIH HHS R01 HL131460NHLBI NIH HHS R01 HL132399
6 · The paper itself

Abstract

backgroundCaspase-1 is present in the cytosol as an inactive zymogen and requires the protein complexes named "inflammasomes" for proteolytic activation. However, it remains unclear whether the proteolytic activity of caspase-1 is confined only to the cytosol where inflammasomes are assembled to convert inactive pro-caspase-1 to active caspase-1.

methodsWe conducted meticulous data analysis methods on proteomic, protein interaction, protein intracellular localization, and gene expressions of 114 experimentally identified caspase-1 substrates and 38 caspase-1 interaction proteins in normal physiological conditions and in various pathologies.

resultsWe made the following important findings: (1) Caspase-1 substrates and interaction proteins are localized in various intracellular organelles including nucleus and secreted extracellularly; (2) Caspase-1 may get activated in situ in the nucleus in response to intra-nuclear danger signals; (3) Caspase-1 cleaves its substrates in exocytotic secretory pathways including exosomes to propagate inflammation to neighboring and remote cells; (4) Most of caspase-1 substrates are upregulated in coronary artery disease regardless of their subcellular localization but the majority of metabolic diseases cause no significant expression changes in caspase-1 nuclear substrates; and (5) In coronary artery disease, majority of upregulated caspase-1 extracellular substrate-related pathways are involved in induction of inflammation; and in contrast, upregulated caspase-1 nuclear substrate-related pathways are more involved in regulating cell death and chromatin regulation.

conclusionsOur identification of novel caspase-1 trafficking sites, nuclear and extracellular inflammasomes, and extracellular caspase-1-based inflammation propagation model provides a list of targets for the future development of new therapeutics to treat cardiovascular diseases, inflammatory diseases, and inflammatory cancers.

Indexed as

Gene Expression RegulationInflammationAnimalsCaspase 1Cell DeathCell NucleusChromatinCoronary Artery DiseaseData MiningHumansInflammasomesOrganellesCaspase 1ChromatinInflammasomesCaspase-1ExosomeInflammation propagationNuclear gene regulationTrafficking

Identifiers

PMID27842563
PMCPMC5109738
OpenAlexW2552379875

What OpenQuestion holds

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LicenceCC BY
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.