Evidence map›Paper›PMID 35984546›Full record

ArticleAngiogenesis2023

Protein disulfide isomerase A1 as a novel redox sensor in VEGFR2 signaling and angiogenesis.

Sheela Nagarkoti, Young-Mee Kim, Dipankar Ash, Archita Das, Eric Vitriol, Tracy-Ann Read, Seock-Won Youn, Varadarajan Sudhahar, Malgorzata McMenamin, Yali Hou and 6 more

Open access · greenAbstract read
In one paragraph

Article in Angiogenesis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.9field-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

10 citing papers in PubMed, 16 citations in OpenAlex.

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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

16 authors at 3 institutions in 1 country.

Sheela Nagarkoti *Vascular Biology Center, Medical College of Georgia at Augusta University, 1460 Laney-Walker Blvd, Augusta, GA, 30912, USA.
Young-Mee Kim *Vascular Biology Center, Medical College of Georgia at Augusta University, 1460 Laney-Walker Blvd, Augusta, GA, 30912, USA.
Dipankar AshVascular Biology Center, Medical College of Georgia at Augusta University, 1460 Laney-Walker Blvd, Augusta, GA, 30912, USA.
Archita DasVascular Biology Center, Medical College of Georgia at Augusta University, 1460 Laney-Walker Blvd, Augusta, GA, 30912, USA.
Eric VitriolNeuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA.
Tracy-Ann ReadNeuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA.
Seock-Won YounVascular Biology Center, Medical College of Georgia at Augusta University, 1460 Laney-Walker Blvd, Augusta, GA, 30912, USA.
Varadarajan SudhaharVascular Biology Center, Medical College of Georgia at Augusta University, 1460 Laney-Walker Blvd, Augusta, GA, 30912, USA.
Malgorzata McMenaminVascular Biology Center, Medical College of Georgia at Augusta University, 1460 Laney-Walker Blvd, Augusta, GA, 30912, USA.
Yali HouVascular Biology Center, Medical College of Georgia at Augusta University, 1460 Laney-Walker Blvd, Augusta, GA, 30912, USA.
Harriet BoatwrightVascular Biology Center, Medical College of Georgia at Augusta University, 1460 Laney-Walker Blvd, Augusta, GA, 30912, USA.
Ruth CaldwellVascular Biology Center, Medical College of Georgia at Augusta University, 1460 Laney-Walker Blvd, Augusta, GA, 30912, USA.
David W EssexDepartment of Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
Jaehyung ChoDivision of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Tohru FukaiVascular Biology Center, Medical College of Georgia at Augusta University, 1460 Laney-Walker Blvd, Augusta, GA, 30912, USA.
Masuko Ushio-FukaiVascular Biology Center, Medical College of Georgia at Augusta University, 1460 Laney-Walker Blvd, Augusta, GA, 30912, USA. mfukai@augusta.edu.ORCID 0000-0001-7048-2381
Augusta University · USTemple University · USWashington University in St. Louis · US

Funding

Cellular Mechanisms of Retinopathy: Role of ArginaseR01EY011766 · NEI · MEDICAL COLLEGE OF GEORGIA (MCG) · PI CALDWELL, ROBERT WILLIAM, CALDWELL, RUTH B · 1998 to 2021
$6.7M
Functional Role of Protein Disulfide Isomerase Isoforms in PlateletsR01HL118526 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI ESSEX, DAVID W · 2013 to 2021
$4.4M
Vascular Extracellular Superoxide Dismutase ModulationR01HL070187 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI FUKAI, TOHRU · 2002 to 2017
$4.2M
Thiol isomerases in neutrophil recruitment and thromboinflammatory diseaseR01HL130028 · NHLBI · WASHINGTON UNIVERSITY · PI CHO, JAEHYUNG · 2016 to 2024
$3.6M
Redox Regulation of Cu Importer CTR1 in AngiogenesisR01HL147550 · NHLBI · AUGUSTA UNIVERSITY · PI FUKAI, TOHRU, USHIO-FUKAI, MASUKO · 2020 to 2023
$3.3M
Copper transport protein and inflammatory angiogenesisR01HL116976 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI FUKAI, TOHRU, USHIO-FUKAI, MASUKO · 2013 to 2016
$2.9M
Cu Transporting ATPase and Diabetic Vascular ComplicationsR01HL133613 · NHLBI · AUGUSTA UNIVERSITY · PI FUKAI, TOHRU, USHIO-FUKAI, MASUKO · 2017 to 2020
$2.7M
Myeloid glycolysis in pathological ocular angiogenesisR01EY030500 · NEI · AUGUSTA UNIVERSITY · PI CALDWELL, RUTH B, HUO, YUQING · 2019 to 2023
$2.6M
Mitochondria Dynamics Protein Drp1 in ROS Signaling, Endothelial Metabolism and AngiogenesisR01HL160014 · NHLBI · AUGUSTA UNIVERSITY · PI USHIO-FUKAI, MASUKO · 2021 to 2024
$2.0M
Thiol isomerases and ERO1α in sickle cell vaso-occlusionR01HL148280 · NHLBI · WASHINGTON UNIVERSITY · PI CHO, JAEHYUNG · 2019 to 2022
$1.9M
Ero1α in platelet activity and thrombosisR01HL146559 · NHLBI · WASHINGTON UNIVERSITY · PI CHO, JAEHYUNG · 2020 to 2023
$1.7M
Role of intravascular ERO1@ in acute lung injuryR01HL153047 · NHLBI · WASHINGTON UNIVERSITY · PI CHO, JAEHYUNG · 2020 to 2023
$1.6M
American Heart Association-American Stroke Association 937665American Heart Association-American Stroke Association 971863BLRD VA I01 BX001232BLRD VA I01 BX001233BLRD VA IK6 BX005228NEI NIH HHS R01 EY011766NEI NIH HHS R01 EY030500NEI NIH HHS R21 EY032265NHLBI NIH HHS R01 HL070187NHLBI NIH HHS R01 HL116976NHLBI NIH HHS R01 HL118526NHLBI NIH HHS R01 HL130028NHLBI NIH HHS R01 HL133613NHLBI NIH HHS R01 HL135584NHLBI NIH HHS R01 HL146559NHLBI NIH HHS R01 HL147550NHLBI NIH HHS R01 HL148280NHLBI NIH HHS R01 HL153047NHLBI NIH HHS R01 HL160014
6 · The paper itself

Abstract

VEGFR2 signaling in endothelial cells (ECs) is regulated by reactive oxygen species (ROS) derived from NADPH oxidases (NOXs) and mitochondria, which plays an important role in postnatal angiogenesis. However, it remains unclear how highly diffusible ROS signal enhances VEGFR2 signaling and reparative angiogenesis. Protein disulfide isomerase A1 (PDIA1) functions as an oxidoreductase depending on the redox environment. We hypothesized that PDIA1 functions as a redox sensor to enhance angiogenesis. Here we showed that PDIA1 co-immunoprecipitated with VEGFR2 or colocalized with either VEGFR2 or an early endosome marker Rab5 at the perinuclear region upon stimulation of human ECs with VEGF. PDIA1 silencing significantly reduced VEGF-induced EC migration, proliferation and spheroid sprouting via inhibiting VEGFR2 signaling. Mechanistically, VEGF stimulation rapidly increased Cys-OH formation of PDIA1 via the NOX4-mitochondrial ROS axis. Overexpression of "redox-dead" mutant PDIA1 with replacement of the active four Cys residues with Ser significantly inhibited VEGF-induced PDIA1-CysOH formation and angiogenic responses via reducing VEGFR2 phosphorylation. Pdia1

Indexed as

Endothelial CellsProtein Disulfide-IsomerasesAnimalsHumansHydrogen PeroxideIschemiaMiceNeovascularization, PhysiologicOxidation-ReductionReactive Oxygen SpeciesVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Hydrogen PeroxideProtein Disulfide-IsomerasesReactive Oxygen SpeciesVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2AngiogenesisEndothelial cellProtein disulfide isomerase A1Redox signalingVascular endothelial cell growth factor

Identifiers

PMID35984546
PMCPMC9918675
OpenAlexW4292315092

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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.