Evidence map›Paper›PMID 16794260›Full record

ArticleAmerican journal of respiratory cell and molecular biology2006

Induction of the plasminogen activator system by mechanical stimulation of human bronchial epithelial cells.

Eric K Chu, Jason Cheng, John S Foley, Brigham H Mecham, Caroline A Owen, Kathleen J Haley, Thomas J Mariani, Isaac S Kohane, Daniel J Tschumperlin, Jeffrey M Drazen

Open access · greenAbstract read
In one paragraph

Article in American journal of respiratory cell and molecular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 7% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Endothelial Dysfunction in Neurodegenerative Diseases.International journal of molecular sciences · 2023
    Review
  10. Airway mechanical compression: its role in asthma pathogenesis and progression.European respiratory review : an official journal of the European Respiratory Society · 2020
    Review
  11. Irradiation Induces Epithelial Cell Unjamming.Frontiers in cell and developmental biology · 2020
    Article
  12. Article
  13. Article
  14. Article
  15. Asthma.Nature reviews. Disease primers · 2015
    Review
  16. Putting the Squeeze on Airway Epithelia.Physiology (Bethesda, Md.) · 2015
    Review
  17. Article
  18. Review
  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

10 authors at 1 institution in 1 country.

Eric K ChuBrigham and Women's Hospital, Department of Pulmonary and Critical Care Medicine, Harvard School of Public Health, Physiology Program and Children's Hospital Informatics Program, Boston, Massachusetts 02115, USA. e.chu@utoronto.ca
Jason Cheng
John S Foley
Brigham H Mecham
Caroline A Owen
Kathleen J Haley
Thomas J Mariani
Isaac S Kohane
Daniel J Tschumperlin
Jeffrey M Drazen
Brigham and Women's Hospital · US

Funding

RESISTANCE OF THE CELL TO SHAPE DISTORTION--BASIS OF CYTOSKELETAL MECHANICSP01HL033009 · NHLBI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI FREDBERG, JEFFREY J · 1985 to 2005
$10.0M
Novel Roles for MMP-8 in Acute Lung InjuryR01HL063137 · NHLBI · UNIVERSITY OF UTAH · PI OWEN, CAROLINE A · 1999 to 2008
$2.6M
Novel Roles for ADAM15 in Acute Lung InjuryR01HL086814 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI OWEN, CAROLINE A · 2007 to 2010
$1.6M
NHLBI NIH HHS HL-33009NHLBI NIH HHS R01 HL063137NHLBI NIH HHS R01 HL086814
6 · The paper itself

Abstract

Mechanical stimulation of the airway epithelium, as would occur during bronchoconstriction, is a potent stimulus and can activate profibrotic pathways. We used DNA microarray technology to examine gene expression in compressed normal human bronchial epithelial cells (NHBE). Compressive stress applied continuously over an 8-h period to NHBE cells led to the upregulation of several families of genes, including a family of plasminogen-related genes that were previously not known to be regulated in this system. Real-time PCR demonstrated a peak increase in gene expression of 8.0-fold for urokinase plasminogen activator (uPA), 16.2-fold for urokinase plasminogen activator receptor (uPAR), 4.2-fold for plasminogen activator inhibitor-1 (PAI-1), and 3.9-fold for tissue plasminogen activator (tPA). Compressive stress also increased uPA protein levels in the cell lysates (112.0 versus 82.0 ng/ml, P = 0.0004), and increased uPA (4.7 versus 3.3 ng/ml, P = 0.02), uPAR (1.3 versus 0.86 ng/ml, P = 0.007), and PAI-1 (50 versus 36 ng/ml, P = 0.006) protein levels in cell culture media. Functional studies demonstrated increased urokinase-dependent plasmin generation in compression-stimulated cells (0.0090 versus 0.0033 OD/min, P = 0.03). In addition, compression led to increased activation of matrix metalloproteinase (MMP)-9 and MMP-2 in a urokinase-dependent manner. In postmortem human lung tissue, we observed an increase in epithelial uPA and uPAR immunostaining in the airways of two patients who died in status asthmaticus compared with minimal immunoreactivity noted in airways from seven lung donors without asthma. Together these observations suggest an integrated response of airway epithelial cells to mechanical stimulation, acting through the plasminogen-activating system to modify the airway microenvironment.

Indexed as

Up-RegulationAsthmaBronchiBronchoconstrictionCell LineCluster AnalysisEnzyme ActivationEpithelial CellsFibrinolysinGene Expression ProfilingHumansLungMatrix Metalloproteinase 2Matrix Metalloproteinase 9Oligonucleotide Array Sequence AnalysisPlasminogenFibrinolysinMatrix Metalloproteinase 2Matrix Metalloproteinase 9PlasminogenPlasminogen Activator Inhibitor 1PLAUR protein, humanReceptors, Cell SurfaceReceptors, Urokinase Plasminogen ActivatorRNA, MessengerSERPINE1 protein, humanTissue Plasminogen ActivatorUrokinase-Type Plasminogen Activator

Identifiers

PMID16794260
PMCPMC2643292
OpenAlexW1986658649

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.