Evidence map›Paper›PMID 24265314›Full record

ArticleThe Journal of biological chemistry2013

Protein kinase D promotes airway epithelial barrier dysfunction and permeability through down-regulation of claudin-1.

Huachen Gan, Guibo Wang, Qin Hao, Q Jane Wang, Hua Tang

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.7field-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

23 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. A Single-Cell Atlas of Large and Small Airways at Birth in a Porcine Model of Cystic Fibrosis.American journal of respiratory cell and molecular biology · 2022
    Article
  6. Review
  7. Article
  8. The Epithelial Cell Leak Pathway.International journal of molecular sciences · 2021
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Disruption of the airway epithelial barrier in a murine model of respiratory syncytial virus infection.American journal of physiology. Lung cellular and molecular physiology · 2019
    Article
  15. Article
  16. Article
  17. Airborne Particulate Matter Induces Nonallergic Eosinophilic Sinonasal Inflammation in Mice.American journal of respiratory cell and molecular biology · 2017
    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

5 authors at 2 institutions in 1 country.

Huachen GanFrom the Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas 75708 and.
Guibo Wang
Qin Hao
Q Jane Wang
Hua Tang
The University of Texas Health Science Center at Tyler · USUniversity of Pittsburgh · US

Funding

Development of small molecule inhibitors of protein kinase DR01CA142580 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WANG, QIMING JANE · 2010 to 2014
$1.5M
PKD Family Kinase Function and Signaling in Lung FibroblastsR21HL097216 · NHLBI · UNIVERSITY OF TEXAS HLTH CTR AT TYLER · PI TANG, HUA · 2011 to 2012
$378k
NCI NIH HHS R01 CA142580NHLBI NIH HHS R21 HL097216NHLBI NIH HHS R21-HL097216
6 · The paper itself

Abstract

At the interface between host and external environment, the airway epithelium serves as a major protective barrier. In the present study we show that protein kinase D (PKD) plays an important role in the formation and integrity of the airway epithelial barrier. Either inhibition of PKD activity or silencing of PKD increased transepithelial electrical resistance (TEER), resulting in a tighter epithelial barrier. Among the three PKD isoforms, PKD3 knockdown was the most efficient one to increase TEER in polarized airway epithelial monolayers. In contrast, overexpression of PKD3 wild type, but not PKD3 kinase-inactive mutant, disrupted the formation of apical intercellular junctions and their reassembly, impaired the development of TEER, and increased paracellular permeability to sodium fluorescein in airway epithelial monolayers. We further found that overexpression of PKD, in particular PKD3, markedly suppressed the mRNA and protein levels of claudin-1 but had only minor effects on the expression of other tight junctional proteins (claudin-3, claudin-4, claudin-5, occludin, and ZO-1) and adherent junctional proteins (E-cadherin and β-catenin). Immunofluorescence study revealed that claudin-1 level was markedly reduced and almost disappeared from intercellular contacts in PKD3-overexpressed epithelial monolayers and that claudin-4 was also restricted from intercellular contacts and tended to accumulate in the cell cytosolic compartments. Last, we found that claudin-1 knockdown prevented TEER elevation by PKD inhibition or silencing in airway epithelial monolayers. These novel findings indicate that PKD negatively regulates human airway epithelial barrier formation and integrity through down-regulation of claudin-1, which is a key component of tight junctions.

Indexed as

Down-RegulationBlood-Air BarrierCells, CulturedClaudin-1Electric ImpedanceEpithelial CellsGene Knockdown TechniquesHumansPermeabilityProtein Kinase CRespiratory MucosaRNA, MessengerTight JunctionsClaudin-1CLDN1 protein, humanProtein Kinase Cprotein kinase DRNA, MessengerCell JunctionsClaudin-1Epithelial CellPermeabilityProtein Kinase D (PKD)Tight Junctions

Identifiers

PMID24265314
PMCPMC3873586
OpenAlexW2011269589

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.