Evidence map›Paper›PMID 22413019›Full record

ArticlePloS one2012

A disintegrin and metalloenzyme (ADAM) 17 activation is regulated by α5β1 integrin in kidney mesangial cells.

Pal Gooz, Yujing Dang, Shigeki Higashiyama, Waleed O Twal, Courtney J Haycraft, Monika Gooz

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.0field-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

21 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Thy-1-Integrin Interactions inFrontiers in cell and developmental biology · 2022
    Review
  7. Article
  8. Review
  9. Article
  10. Substrate-selective protein ectodomain shedding by ADAM17 and iRhom2 depends on their juxtamembrane and transmembrane domains.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  11. Review
  12. Multiple non-catalytic ADAMs are novel integrin α4 ligands.Molecular and cellular biochemistry · 2018
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. 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

6 authors at 2 institutions in 2 countries.

Pal GoozDepartment of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
Yujing Dang
Shigeki Higashiyama
Waleed O Twal
Courtney J Haycraft
Monika Gooz
Medical University of South Carolina · USEhime University · JP

Funding

Crosstalk among Growth Factors, ADAMs and IntegrinsK01DK070054 · NIDDK · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI GOOZ, MONIKA · 2005 to 2010
$587k
NIDDK NIH HHS 3K01DK070054-05S1NIDDK NIH HHS K01 DK070054
6 · The paper itself

Abstract

backgroundThe disintegrin and metalloenzyme ADAM17 participates in numerous inflammatory and proliferative diseases, and its pathophysiological role was implicated in kidney fibrosis, polycystic kidney disease and other chronic kidney diseases. At present, we have little understanding how the enzyme activity is regulated. In this study we wanted to characterize the role of α5β1 integrin in ADAM17 activity regulation during G protein-coupled receptor (GPCR) stimulation. METHODOLOGY/PRINCIPAL

findingsWe showed previously that the profibrotic GPCR agonist serotonin (5-HT) induced kidney mesangial cell proliferation through ADAM17 activation and heparin-binding epidermal growth factor (HB-EGF) shedding. In the present studies we observed that in unstimulated mesangial cell lysates α5β1 integrin co-precipitated with ADAM17 and that 5-HT treatment of the cells induced dissociation of α5β1 integrin from ADAM17. Using fluorescence immunostaining and in situ proximity ligation assay, we identified the perinuclear region as the localization of the ADAM17/α5β1 integrin interaction. In cell-free assays, we showed that purified α5β1 integrin and β1 integrin dose-dependently bound to and inhibited activity of recombinant ADAM17. We provided evidence that the conformation of the integrin determines its ADAM17-binding ability. To study the effect of β1 integrin on ADAM17 sheddase activity, we employed alkaline phosphatase-tagged HB-EGF. Overexpression of β1 integrin lead to complete inhibition of 5-HT-induced HB-EGF shedding and silencing β1 integrin by siRNA significantly increased mesangial cells ADAM17 responsiveness to 5-HT. CONCLUSIONS/SIGNIFICANCE: Our data show for the first time that β1 integrin has an important physiological role in ADAM17 activity regulation. We suggest that regulating α5β1 integrin binding to ADAM17 could be an attractive therapeutic target in chronic kidney diseases.

Indexed as

ADAM17 ProteinADAM ProteinsAnimalsCells, CulturedEnzyme ActivationHeparin-binding EGF-like Growth FactorIntegrin alpha5beta1Integrin beta1Intercellular Signaling Peptides and ProteinsMesangial CellsMultiprotein ComplexesProtein BindingProtein TransportRatsRats, Sprague-DawleyReceptors, G-Protein-Coupled5-(3-hydroxybenzoyl)-2-thiophenesulfonamideADAM17 ProteinAdam17 protein, ratADAM ProteinsHbegf protein, ratHeparin-binding EGF-like Growth FactorIntegrin alpha5beta1Integrin beta1Intercellular Signaling Peptides and ProteinsMultiprotein ComplexesReceptors, G-Protein-CoupledThiophenes

Identifiers

PMID22413019
PMCPMC3297637
OpenAlexW1969333571

What OpenQuestion holds

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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.