Evidence map›Paper›PMID 26839042›Full record

ArticleCirculation2016

Endothelial p110γPI3K Mediates Endothelial Regeneration and Vascular Repair After Inflammatory Vascular Injury.

Xiaojia Huang, Zhiyu Dai, Lei Cai, Kai Sun, Jaehyung Cho, Kurt H Albertine, Asrar B Malik, Dean E Schraufnagel, You-Yang Zhao

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
3.5field-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

49 citing papers in PubMed, 72 citations in OpenAlex.

  1. Article
  2. Review
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  4. Article
  5. Article
  6. Regulation of inflammatory lung injury and repair by transforming growth factors.American journal of physiology. Lung cellular and molecular physiology · 2025
    Review
  7. Article
  8. Review
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  11. Article
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  13. Article
  14. Article
  15. ISGylation of NF-κBp65 by SCFArteriosclerosis, thrombosis, and vascular biology · 2023
    Article
  16. Review
  17. Article
  18. Article
  19. Article
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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

9 authors at 1 institution in 1 country.

Xiaojia HuangFrom Department of Pharmacology (X.H., Z.D., L.C., K.S., J.C., A.B.M., Y.-Y.Z.), Center for Lung and Vascular Biology (X.H., Z.D., L.C., K.S., A.B.M., Y.-Y.Z.), Department of Medicine (D.E.S.), University of Illinois College of Medicine, Chicago; and Departments of Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City (K.H.A.).
Zhiyu DaiFrom Department of Pharmacology (X.H., Z.D., L.C., K.S., J.C., A.B.M., Y.-Y.Z.), Center for Lung and Vascular Biology (X.H., Z.D., L.C., K.S., A.B.M., Y.-Y.Z.), Department of Medicine (D.E.S.), University of Illinois College of Medicine, Chicago; and Departments of Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City (K.H.A.).
Lei CaiFrom Department of Pharmacology (X.H., Z.D., L.C., K.S., J.C., A.B.M., Y.-Y.Z.), Center for Lung and Vascular Biology (X.H., Z.D., L.C., K.S., A.B.M., Y.-Y.Z.), Department of Medicine (D.E.S.), University of Illinois College of Medicine, Chicago; and Departments of Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City (K.H.A.).
Kai SunFrom Department of Pharmacology (X.H., Z.D., L.C., K.S., J.C., A.B.M., Y.-Y.Z.), Center for Lung and Vascular Biology (X.H., Z.D., L.C., K.S., A.B.M., Y.-Y.Z.), Department of Medicine (D.E.S.), University of Illinois College of Medicine, Chicago; and Departments of Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City (K.H.A.).
Jaehyung ChoFrom Department of Pharmacology (X.H., Z.D., L.C., K.S., J.C., A.B.M., Y.-Y.Z.), Center for Lung and Vascular Biology (X.H., Z.D., L.C., K.S., A.B.M., Y.-Y.Z.), Department of Medicine (D.E.S.), University of Illinois College of Medicine, Chicago; and Departments of Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City (K.H.A.).
Kurt H AlbertineFrom Department of Pharmacology (X.H., Z.D., L.C., K.S., J.C., A.B.M., Y.-Y.Z.), Center for Lung and Vascular Biology (X.H., Z.D., L.C., K.S., A.B.M., Y.-Y.Z.), Department of Medicine (D.E.S.), University of Illinois College of Medicine, Chicago; and Departments of Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City (K.H.A.).
Asrar B MalikFrom Department of Pharmacology (X.H., Z.D., L.C., K.S., J.C., A.B.M., Y.-Y.Z.), Center for Lung and Vascular Biology (X.H., Z.D., L.C., K.S., A.B.M., Y.-Y.Z.), Department of Medicine (D.E.S.), University of Illinois College of Medicine, Chicago; and Departments of Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City (K.H.A.).
Dean E SchraufnagelFrom Department of Pharmacology (X.H., Z.D., L.C., K.S., J.C., A.B.M., Y.-Y.Z.), Center for Lung and Vascular Biology (X.H., Z.D., L.C., K.S., A.B.M., Y.-Y.Z.), Department of Medicine (D.E.S.), University of Illinois College of Medicine, Chicago; and Departments of Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City (K.H.A.).
You-Yang ZhaoFrom Department of Pharmacology (X.H., Z.D., L.C., K.S., J.C., A.B.M., Y.-Y.Z.), Center for Lung and Vascular Biology (X.H., Z.D., L.C., K.S., A.B.M., Y.-Y.Z.), Department of Medicine (D.E.S.), University of Illinois College of Medicine, Chicago; and Departments of Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City (K.H.A.). yyzhao@uic.edu.
University of Utah · US

Funding

TRPC6 Regulation of Lung Endothelial Barrier FunctionP01HL060678 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MALIK, ASRAR B. · 2000 to 2020
$40.1M
Trpm2 Regulation of Phagocyte Bactericidal Activity and Resolution of Lung InjuryP01HL077806 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI ZHAO, YOU-YANG · 2005 to 2019
$27.0M
Repair mechanisms of sepsis induced endothelial dysfunction and lung injuryR01HL125350 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MALIK, ASRAR B., ZHAO, YOU-YANG · 2014 to 2018
$3.2M
Novel Signalings and Molecular Targets Of Endothelial Regeneration In Aging LungR01HL123957 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI ZHAO, YOU-YANG · 2014 to 2018
$2.0M
Protein disulfide isomerase in neutrophil recruitment and vascular inflammationR01HL109439 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI CHO, JAEHYUNG · 2011 to 2015
$2.0M
NHLBI NIH HHS P01 HL060678NHLBI NIH HHS P01 HL077806NHLBI NIH HHS P01HL077806NHLBI NIH HHS R01 HL109439NHLBI NIH HHS R01 HL123957NHLBI NIH HHS R01HL123957NHLBI NIH HHS R01 HL125350NHLBI NIH HHS R01HL125350
6 · The paper itself

Abstract

backgroundThe integrity of endothelial monolayer is a sine qua non for vascular homeostasis and maintenance of tissue-fluid balance. However, little is known about the signaling pathways regulating regeneration of the endothelial barrier after inflammatory vascular injury. METHODS AND

resultsUsing genetic and pharmacological approaches, we demonstrated that endothelial regeneration selectively requires activation of p110γPI3K signaling, which thereby mediates the expression of the endothelial reparative transcription factor Forkhead box M1 (FoxM1). We observed that FoxM1 induction in the pulmonary vasculature was inhibited in mice treated with a p110γ-selective inhibitor and in Pik3cg(-/-) mice after lipopolysaccharide challenge. Pik3cg(-/-) mice exhibited persistent lung inflammation induced by sepsis and sustained increase in vascular permeability. Restoration of expression of either p110γ or FoxM1 in pulmonary endothelial cells of Pik3cg(-/-) mice restored endothelial regeneration and normalized the defective vascular repair program. We also observed diminished expression of p110γ in pulmonary vascular endothelial cells of patients with acute respiratory distress syndrome, suggesting that impaired p110γ-FoxM1 vascular repair signaling pathway is a critical factor in persistent leaky lung microvessels and edema formation in the disease.

conclusionsWe identify p110γ as the critical mediator of endothelial regeneration and vascular repair after sepsis-induced inflammatory injury. Thus, activation of p110γ-FoxM1 endothelial regeneration may represent a novel strategy for the treatment of inflammatory vascular diseases.

Indexed as

AndrostadienesAnimalsCapillary Leak SyndromeCapillary PermeabilityCells, CulturedClass Ib Phosphatidylinositol 3-KinaseEndothelium, VascularEnzyme ActivationEnzyme InductionForkhead Box Protein M1Forkhead Transcription FactorsFuransHumansLungMiceMice, Knockout5-quinoxalin-6-ylmethylenethiazolidine-2,4-dioneAndrostadienesClass Ib Phosphatidylinositol 3-KinaseForkhead Box Protein M1Forkhead Transcription FactorsFoxm1 protein, mouseFuransPhosphoinositide-3 Kinase InhibitorsPI103PIK3CG protein, humanPik3cg protein, mouseProtein IsoformsPyridinesPyrimidinesQuinoxalinesRecombinant Fusion ProteinsThiazolidinedionesWortmanninendothelial regenerationendothelium, vascularinflammationvascular diseasesvascular repair

Identifiers

PMID26839042
PMCPMC4792690
OpenAlexW2252628367

What OpenQuestion holds

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Registered trials

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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.