Evidence map›Paper›PMID 25844601›Full record

ArticleOncotarget2015

Aquaporin 1 and 5 expression decreases during human intervertebral disc degeneration: Novel HIF-1-mediated regulation of aquaporins in NP cells.

Zariel I Johnson, Shilpa S Gogate, Rebecca Day, Abbie Binch, Dessislava Z Markova, Neil Chiverton, Ashley Cole, Matt Conner, Irving M Shapiro, Christine L Le Maitre and 1 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 16% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Aquaporin-5 Dynamic Regulation.International journal of molecular sciences · 2023
    Review
  5. Aquaporins in Reproductive System.Advances in experimental medicine and biology · 2023
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Hyperosmolarity induces notochordal cell differentiation with aquaporin3 upregulation and reduced N-cadherin expression.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2018
    Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
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

11 authors at 3 institutions in 2 countries.

Zariel I JohnsonDepartment of Orthopaedic Surgery and Graduate Program in Cell and Developmental Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Shilpa S GogateDepartment of Orthopaedic Surgery and Graduate Program in Cell and Developmental Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Rebecca DayBiomedical Research Centre, Sheffield Hallam University, Sheffield, UK.
Abbie BinchBiomedical Research Centre, Sheffield Hallam University, Sheffield, UK.
Dessislava Z MarkovaDepartment of Orthopaedic Surgery and Graduate Program in Cell and Developmental Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Neil ChivertonSheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
Ashley ColeSheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
Matt ConnerBiomedical Research Centre, Sheffield Hallam University, Sheffield, UK.
Irving M ShapiroDepartment of Orthopaedic Surgery and Graduate Program in Cell and Developmental Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Christine L Le MaitreBiomedical Research Centre, Sheffield Hallam University, Sheffield, UK.
Makarand V RisbudDepartment of Orthopaedic Surgery and Graduate Program in Cell and Developmental Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Thomas Jefferson University · USSheffield Hallam University · GBSheffield Teaching Hospitals NHS Foundation Trust · GB

Funding

X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI Andrew Chapman · 1995 to 2026
$94.8M
Role of HIF-1 in Intervertebral Disc FunctionR01AR055655 · NIAMS · THOMAS JEFFERSON UNIVERSITY · PI RISBUD, MAKARAND V · 2008 to 2023
$6.1M
Training in Tissue Engineering and Regenerative MedicineT32AR052273 · NIAMS · THOMAS JEFFERSON UNIVERSITY · PI SHAPIRO, IRVING M · 2006 to 2020
$3.3M
Regeneration of Nucleus Pulposus by Tissue EngineeringR01AR050087 · NIAMS · THOMAS JEFFERSON UNIVERSITY · PI RISBUD, MAKARAND V, SHAPIRO, IRVING M · 2005 to 2013
$3.0M
Disruption of Osmoregulation Promotes Degenerative Disc DiseaseR01AR064733 · NIAMS · THOMAS JEFFERSON UNIVERSITY · PI RISBUD, MAKARAND V, SHAPIRO, IRVING M · 2014 to 2018
$2.4M
NCI NIH HHS P30 CA056036NIAMS NIH HHS AR050087NIAMS NIH HHS AR055655NIAMS NIH HHS AR064733NIAMS NIH HHS R01 AR050087NIAMS NIH HHS R01 AR055655NIAMS NIH HHS R01 AR064733NIAMS NIH HHS T32 AR052273
6 · The paper itself

Abstract

Objectives of this study were to investigate whether AQP1 and AQP5 expression is altered during intervertebral disc degeneration and if hypoxia and HIF-1 regulate their expression in NP cells. AQP expression was measured in human tissues from different degenerative grades; regulation by hypoxia and HIF-1 was studied using promoter analysis and gain- and loss-of-function experiments. We show that both AQPs are expressed in the disc and that mRNA and protein levels decline with human disease severity. Bioinformatic analyses of AQP promoters showed multiple evolutionarily conserved HREs. Surprisingly, hypoxia failed to induce promoter activity or expression of either AQP. While genomic chromatin immunoprecipitation showed limited binding of HIF-1α to conserved HREs, their mutation did not suppress promoter activities. Stable HIF-1α suppression significantly decreased mRNA and protein levels of both AQPs, but HIF-1α failed to induce AQP levels following accumulation. Together, our results demonstrate that AQP1 and AQP5 expression is sensitive to human disc degeneration and that HIF-1α uniquely maintains basal expression of both AQPs in NP cells, independent of oxemic tension and HIF-1 binding to promoter HREs. Diminished HIF-1 activity during degeneration may suppress AQP levels in NP cells, compromising their ability to respond to extracellular osmolarity changes.

Indexed as

AnimalsAquaporin 1Aquaporin 5Blotting, WesternCell HypoxiaChromatin ImmunoprecipitationGene Expression RegulationHumansHypoxia-Inducible Factor 1, alpha SubunitImmunohistochemistryIntervertebral Disc DegenerationMicroscopy, FluorescenceRatsReal-Time Polymerase Chain ReactionResponse ElementsTransfectionAQP5 protein, humanAquaporin 1Aquaporin 5HIF1A protein, humanHypoxia-Inducible Factor 1, alpha Subunitaquaporin 1aquaporin 5HIF-1intervertebral discnucleus pulposusPathology Section

Identifiers

PMID25844601
PMCPMC4494915
OpenAlexW2116026951

What OpenQuestion holds

Textmetadata
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.