Evidence map›Paper›PMID 26634653›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2016

Antithrombotic Effects of Nur77 and Nor1 Are Mediated Through Upregulating Thrombomodulin Expression in Endothelial Cells.

Ping Yang, Xin Wei, Jian Zhang, Bing Yi, Guan-Xin Zhang, Litian Yin, Xiao-Feng Yang, Jianxin Sun

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.3field-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

16 citing papers in PubMed, 27 citations in OpenAlex.

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  13. Reporting Sex and Sex Differences in Preclinical Studies.Arteriosclerosis, thrombosis, and vascular biology · 2018
    Article
  14. Article
  15. Thrombotic Regulation From the Endothelial Cell Perspectives.Arteriosclerosis, thrombosis, and vascular biology · 2018
    Review
  16. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Ping YangFrom the Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, China (P.Y., X.W., J.Z.); Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (P.Y., X.W., B.Y., G-.X.Z.,L.Y., J.S.); and Centers of Metabolic Disease Research and Cardiovascular Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (X-.F.Y.).
Xin WeiFrom the Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, China (P.Y., X.W., J.Z.); Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (P.Y., X.W., B.Y., G-.X.Z.,L.Y., J.S.); and Centers of Metabolic Disease Research and Cardiovascular Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (X-.F.Y.).
Jian ZhangFrom the Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, China (P.Y., X.W., J.Z.); Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (P.Y., X.W., B.Y., G-.X.Z.,L.Y., J.S.); and Centers of Metabolic Disease Research and Cardiovascular Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (X-.F.Y.).
Bing YiFrom the Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, China (P.Y., X.W., J.Z.); Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (P.Y., X.W., B.Y., G-.X.Z.,L.Y., J.S.); and Centers of Metabolic Disease Research and Cardiovascular Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (X-.F.Y.).
Guan-Xin ZhangFrom the Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, China (P.Y., X.W., J.Z.); Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (P.Y., X.W., B.Y., G-.X.Z.,L.Y., J.S.); and Centers of Metabolic Disease Research and Cardiovascular Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (X-.F.Y.).
Litian YinFrom the Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, China (P.Y., X.W., J.Z.); Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (P.Y., X.W., B.Y., G-.X.Z.,L.Y., J.S.); and Centers of Metabolic Disease Research and Cardiovascular Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (X-.F.Y.).
Xiao-Feng YangFrom the Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, China (P.Y., X.W., J.Z.); Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (P.Y., X.W., B.Y., G-.X.Z.,L.Y., J.S.); and Centers of Metabolic Disease Research and Cardiovascular Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (X-.F.Y.).
Jianxin SunFrom the Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, China (P.Y., X.W., J.Z.); Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA (P.Y., X.W., B.Y., G-.X.Z.,L.Y., J.S.); and Centers of Metabolic Disease Research and Cardiovascular Research, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (X-.F.Y.). jianxin.sun@jefferson.edu.
XinHua Hospital · CN

Funding

Regulation of Endothelial Nitric Oxide Synthase mRNA StabilityR01HL103869 · NHLBI · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI SUN, JIANXIN · 2010 to 2020
$3.5M
Caspase-1 activation mediates chronic kidney disease-accelerated atherosclerosisR01HL131460 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI CHOI, ERIC T., WANG, HONG · 2016 to 2019
$2.8M
IL-35 suppression of endothelial cell activation and atherosclerosisR01HL132399 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI YANG, XIAOFENG · 2017 to 2020
$2.3M
Roles of Interleukin-17 in Endothelial CellsR01HL108910 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI YANG, XIAOFENG · 2011 to 2015
$1.9M
Suppression of vascular endothelial cell inflammationR01HL094451 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI YANG, XIAOFENG · 2009 to 2013
$1.8M
HHcy-induced Bax upregulation, Treg apoptosis and vascular diseaseR01HL116917 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI YANG, XIAOFENG · 2013 to 2016
$1.6M
NHLBI NIH HHS HL103869NHLBI NIH HHS R01 HL094451NHLBI NIH HHS R01 HL103869NHLBI NIH HHS R01 HL108910NHLBI NIH HHS R01 HL116917NHLBI NIH HHS R01 HL131460NHLBI NIH HHS R01 HL132399
6 · The paper itself

Abstract

objectiveThrombomodulin is highly expressed on the lumenal surface of vascular endothelial cells (ECs) and possesses potent anticoagulant, antifibrinolytic, and anti-inflammatory activities in the vessel wall. However, the regulation of thrombomodulin expression in ECs remains largely unknown. APPROACHES AND

resultsIn this study, we characterized nuclear receptor 4A family as a novel regulator of thrombomodulin expression in vascular ECs. We demonstrated that both nuclear receptors 4A, Nur77 and Nor1, robustly increase thrombomodulin mRNA and protein levels in human vascular ECs and in mouse liver tissues after adenovirus-mediated transduction of Nur77 and Nor1 cDNAs. Moreover, Nur77 deficiency and knockdown of Nur77 and Nor1 expression markedly attenuated the basal and vascular endothelial growth factor165-stimulated thrombomodulin expression. Mechanistically, we found that Nur77 and Nor1 increase thrombomodulin expression by acting through 2 different mechanisms. We showed that Nur77 barely affects thrombomodulin promoter activity, but significantly increases thrombomodulin mRNA stability, whereas Nor1 enhances thrombomodulin expression mainly through induction of Kruppel-like factors 2 and 4 in vascular ECs. Furthermore, we demonstrated that both Nur77 and Nor1 significantly increase protein C activity and inhibit tumor necrosis factor α-induced prothrombotic effects in human ECs. Deficiency of Nur77 increases susceptibility to arterial thrombosis, whereas enhanced expression of Nur77 and Nor1 protects mice from arterial thrombus formation.

conclusionsOur results identified nuclear receptors 4A as novel regulators of thrombomodulin expression and function in vascular ECs and provided a proof-of-concept demonstration that targeted increasing expression of Nur77 and Nor1 in the vascular endothelium might represent a novel therapeutic approach for the treatment of thrombotic disorders.

Indexed as

AnimalsBlood CoagulationCarotid StenosisCells, CulturedDisease Models, AnimalDNA-Binding ProteinsHumansHuman Umbilical Vein Endothelial CellsMaleMice, Inbred C57BLNerve Tissue ProteinsNuclear Receptor Subfamily 4, Group A, Member 1Promoter Regions, GeneticProtein CReceptors, SteroidReceptors, Thyroid HormoneDNA-Binding ProteinsNerve Tissue ProteinsNR4A1 protein, humanNr4a1 protein, mouseNR4A3 protein, humanNr4a3 protein, mouseNuclear Receptor Subfamily 4, Group A, Member 1Protein CReceptors, SteroidReceptors, Thyroid HormoneRNA, MessengerTHBD protein, humanTHBD protein, mouseThrombomodulinanticoagulantsendothelial cellsthrombomodulinthrombosistumor necrosis factor

Identifiers

PMID26634653
PMCPMC5113034
OpenAlexW2258271733

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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.