Evidence map›Paper›PMID 24500283›Full record

ArticleAmerican journal of physiology. Cell physiology2014

Reduced GM1 ganglioside in CFTR-deficient human airway cells results in decreased β1-integrin signaling and delayed wound repair.

Yutaka Itokazu, Richard E Pagano, Andreas S Schroeder, Scott M O'Grady, Andrew H Limper, David L Marks

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Cell physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

30 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
  2. Ion channels and actin: A tale of two friends.Histology and histopathology · 2025
    Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. CFTR, Cell Junctions and the Cytoskeleton.International journal of molecular sciences · 2022
    Review
  11. Article
  12. Article
  13. Pathophysiology of Lung Disease and Wound Repair in Cystic Fibrosis.Pathophysiology : the official journal of the International Society for Pathophysiology · 2021
    Review
  14. Article
  15. Proteomics and Metabolomics for Cystic Fibrosis Research.International journal of molecular sciences · 2020
    Review
  16. GM1 as Adjuvant of Innovative Therapies for Cystic Fibrosis Disease.International journal of molecular sciences · 2020
    Article
  17. Review
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Yutaka ItokazuThoracic Diseases Research Unit, Division of Pulmonary and Critical Care Medicine, Mayo Clinic and Foundation, Rochester, Minnesota;
Richard E Pagano
Andreas S Schroeder
Scott M O'Grady
Andrew H Limper
David L Marks
Mayo Clinic · USCharlie Norwood VA Medical Center · USUniversity of Minnesota · US

Funding

MAYO CLINIC CENTER FOR TRANSLATIONAL SCIENCE ACTIVITIESUL1RR024150 · NCRR · MAYO CLINIC ROCHESTER · PI RIZZA, ROBERT A. · 2006 to 2011
$66.4M
MEMBRANE TRAFFIC IN SPHINGOLIPID STORAGE DISEASESR01GM060934 · NIGMS · MAYO CLINIC ROCHESTER · PI LIMPER, ANDREW H · 2001 to 2011
$2.9M
CFTR regulation of airway epithelial cell migrationR21HL095811 · NHLBI · UNIVERSITY OF MINNESOTA · PI O'GRADY, SCOTT M. · 2010 to 2011
$396k
NCRR NIH HHS UL1 RR024150NHLBI NIH HHS HL-095811NIGMS NIH HHS GM60934
6 · The paper itself

Abstract

Loss of cystic fibrosis transmembrane conductance regulator (CFTR) function reduces chloride secretion and increases sodium uptake, but it is not clear why CFTR mutation also results in progressive lung inflammation and infection. We previously demonstrated that CFTR-silenced airway cells migrate more slowly during wound repair than CFTR-expressing controls. In addition, CFTR-deficient cells and mouse models have been reported to have altered sphingolipid levels. Here, we investigated the hypothesis that reduced migration in CFTR-deficient airway epithelial cells results from altered sphingolipid composition. We used cell lines derived from a human airway epithelial cell line (Calu-3) stably transfected with CFTR short hairpin RNA (CFTR-silenced) or nontargeting short hairpin RNA (controls). Cell migration was measured by electric cell substrate impedance sensing (ECIS). Lipid analyses, addition of exogenous glycosphingolipids, and immunoblotting were performed. We found that levels of the glycosphingolipid, GM1 ganglioside, were ~60% lower in CFTR-silenced cells than in controls. CFTR-silenced cells exhibited reduced levels of activated β1-integrin, phosphorylated tyrosine 576 of focal adhesion kinase (pFAK), and phosphorylation of Crk-associated substrate (pCAS). Addition of GM1 (but not GM3) ganglioside to CFTR-silenced cells restored activated β1-integrin, pFAK, and pCAS to near control levels and partially restored (~40%) cell migration. Our results suggest that decreased GM1 in CFTR-silenced cells depresses β1-integrin signaling, which contributes to the delayed wound repair observed in these cells. These findings have implications for the pathology of cystic fibrosis, where altered sphingolipid levels in airway epithelial cells could result in a diminished capacity for wound repair after injury.

Indexed as

Cell MovementWound HealingCell LineCrk-Associated Substrate ProteinCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDown-RegulationElectric ImpedanceEpithelial CellsFocal Adhesion Kinase 1G(M1) GangliosideHumansIntegrin beta1LungPhosphorylationRNA InterferenceBCAR1 protein, humanCFTR protein, humanCrk-Associated Substrate ProteinCystic Fibrosis Transmembrane Conductance RegulatorFocal Adhesion Kinase 1G(M1) GangliosideIntegrin beta1PTK2 protein, humanTyrosinecell attachmentchloride channelspulmonary epithelial cellssialo-lipids

Identifiers

PMID24500283
PMCPMC4010808
OpenAlexW2313722988

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.