Evidence map›Paper›PMID 27442243›Full record

ArticlePloS one2016

Regulation of Thrombin-Induced Lung Endothelial Cell Barrier Disruption by Protein Kinase C Delta.

Lishi Xie, Eddie T Chiang, Xiaomin Wu, Gabriel T Kelly, Prasad Kanteti, Patrick A Singleton, Sara M Camp, Tingting Zhou, Steven M Dudek, Viswanathan Natarajan and 4 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

13 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. PKCδ regulates the vascular biology in diabetic atherosclerosis.Cell communication and signaling : CCS · 2023
    Review
  3. Article
  4. Review
  5. Article
  6. An Actin-, Cortactin- and Ena-VASP-Linked Complex Contributes to Endothelial Cell Focal Adhesion and Vascular Barrier Regulation.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2022
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. IPCellular and molecular life sciences : CMLS · 2017
    Review
  13. 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

14 authors at 3 institutions in 1 country.

Lishi XieInstitute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Eddie T ChiangDepartment of Medicine and Arizona Respiratory Center, University of Arizona, Tucson, Arizona, United States of America.
Xiaomin WuDepartment of Medicine and Arizona Respiratory Center, University of Arizona, Tucson, Arizona, United States of America.ORCID http://orcid.org/0000-0002-8792-0584
Gabriel T KellyDepartment of Medicine and Arizona Respiratory Center, University of Arizona, Tucson, Arizona, United States of America.
Prasad KantetiInstitute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Patrick A SingletonDepartment of Medicine, University of Chicago, Chicago, Illinois, United States of America.
Sara M CampDepartment of Medicine and Arizona Respiratory Center, University of Arizona, Tucson, Arizona, United States of America.
Tingting ZhouInstitute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Steven M DudekInstitute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Viswanathan NatarajanInstitute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Ting WangDepartment of Medicine and Arizona Respiratory Center, University of Arizona, Tucson, Arizona, United States of America.
Steven M BlackDepartment of Medicine and Arizona Respiratory Center, University of Arizona, Tucson, Arizona, United States of America.
Joe G N GarciaInstitute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Jeffrey R JacobsonInstitute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
University of Arizona · USUniversity of Illinois Chicago · USUniversity of Chicago · US

Funding

Tissue Culture Biomechanical CoreP01HL058064 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI LAL, RATNESHWAR · 1998 to 2012
$27.8M
Structure-Function Analysis of nmMLCK in EC Barrier ResponsesP01HL126609 · NHLBI · UNIVERSITY OF FLORIDA · PI Joe G. N. Garcia · 2016 to 2026
$24.4M
PHYSIOLOGYT32HL007249 · NHLBI · UNIVERSITY OF ARIZONA · PI Brett A Colson, JOHN P KONHILAS · 1985 to 2026
$12.5M
Therapeutic Mechanisms of RhoA Inhibition In Acute Lung InjuryP01HL101902 · NHLBI · AUGUSTA UNIVERSITY · PI BLACK, STEPHEN M · 2011 to 2016
$11.2M
Therapeutic Potential of FTY720 Analogues in Lung InjuryP01HL098050 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI NATARAJAN, VISWANATHAN · 2011 to 2015
$10.9M
PERINATAL REGULATION OF THE ENDOTHELIAL NOS GENER01HL060190 · NHLBI · UNIVERSITY OF MONTANA · PI Stephen M Black · 1998 to 2026
$7.1M
Regulation of Asthmatic Inflammation by Non-Muscle MLCKR01HL091889 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI GARCIA, JOE G. N., WANG, TING · 2008 to 2018
$3.2M
ROS in Pulmonary Hypertension: Role of ADMAR01HL067841 · NHLBI · UNIVERSITY OF MONTANA · PI BLACK, STEPHEN M · 2002 to 2011
$2.6M
Integrin Beta 4 in Vascular Inflammatory ResponsesR01HL096887 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI JACOBSON, JEFFREY R · 2009 to 2013
$1.9M
NHLBI NIH HHS P01 HL058064NHLBI NIH HHS P01 HL098050NHLBI NIH HHS P01 HL101902NHLBI NIH HHS P01 HL126609NHLBI NIH HHS R01 HL060190NHLBI NIH HHS R01 HL067841NHLBI NIH HHS R01 HL091889NHLBI NIH HHS R01 HL096887NHLBI NIH HHS T32 HL007249
6 · The paper itself

Abstract

Protein Kinase C (PKC) plays a significant role in thrombin-induced loss of endothelial cell (EC) barrier integrity; however, the existence of more than 10 isozymes of PKC and tissue-specific isoform expression has limited our understanding of this important second messenger in vascular homeostasis. In this study, we show that PKCδ isoform promotes thrombin-induced loss of human pulmonary artery EC barrier integrity, findings substantiated by PKCδ inhibitory studies (rottlerin), dominant negative PKCδ construct and PKCδ silencing (siRNA). In addition, we identified PKCδ as a signaling mediator upstream of both thrombin-induced MLC phosphorylation and Rho GTPase activation affecting stress fiber formation, cell contraction and loss of EC barrier integrity. Our inhibitor-based studies indicate that thrombin-induced PKCδ activation exerts a positive feedback on Rho GTPase activation and contributes to Rac1 GTPase inhibition. Moreover, PKD (or PKCμ) and CPI-17, two known PKCδ targets, were found to be activated by PKCδ in EC and served as modulators of cytoskeleton rearrangement. These studies clarify the role of PKCδ in EC cytoskeleton regulation, and highlight PKCδ as a therapeutic target in inflammatory lung disorders, characterized by the loss of barrier integrity, such as acute lung injury and sepsis.

Indexed as

AcetophenonesBenzopyransEndothelial CellsEnzyme ActivationGene SilencingHumansIntracellular Signaling Peptides and ProteinsLungModels, BiologicalMuscle ProteinsMyosin Light ChainsPhosphoprotein PhosphatasesPhosphorylationProtein Kinase CProtein Kinase C-deltarho GTP-Binding ProteinsAcetophenonesBenzopyransIntracellular Signaling Peptides and ProteinsMuscle ProteinsMyosin Light ChainsPhosphoprotein PhosphatasesPPP1R14A protein, humanProtein Kinase CProtein Kinase C-deltaprotein kinase Drho GTP-Binding ProteinsrottlerinThrombin

Identifiers

PMID27442243
PMCPMC4956111
OpenAlexW2482687058

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.