Evidence map›Paper›PMID 30930165›Full record

ArticleMicrovascular research2019

DLL4 and Jagged1 are angiogenic targets of orphan nuclear receptor TR3/Nur77.

Jin Peng, Shengqiang Zhao, Yan Li, Gengming Niu, Chen Chen, Taiyang Ye, Dezheng Zhao, Huiyan Zeng

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

Article in Microvascular research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 41% 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

4 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. 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

8 authors at 1 institution in 2 countries.

Jin PengCenter for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Radiotherapy and Medical Oncology Department, Zhongnan Hospital, Wuhan University, Wuhan, PR China.
Shengqiang ZhaoCenter for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, PR China.
Yan LiCenter for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, PR China.
Gengming NiuCenter for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
Chen ChenCenter for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Department of Surgery of Breast and Thyroid, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
Taiyang YeCenter for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Department of Obstetrics & Gynecology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200127, PR China.
Dezheng ZhaoCenter for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Huiyan ZengCenter for Vascular Biology Research and Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. Electronic address: hzeng@bidmc.harvard.edu.
Beth Israel Deaconess Medical Center · US

Funding

Regulation of colitis by orphan nuclear receptor Nur77R01DK095873 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ZHAO, DEZHENG · 2013 to 2017
$1.9M
Orphan Nuclear Receptor TR3 in tumor angiogenesis and associated microvessel permR01CA133235 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ZENG, HUIYAN · 2009 to 2013
$1.7M
Orphan nuclear receptor Nur77 and intestinal inflammmationR21DK080970 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ZHAO, DEZHENG · 2009 to 2010
$468k
Targeting orphan nuclear receptor TR3/Nur77 for tumor angiogenesisR03CA191463 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ZENG, HUIYAN · 2015 to 2016
$174k
NCI NIH HHS R01 CA133235NCI NIH HHS R03 CA191463NIDDK NIH HHS R01 DK095873NIDDK NIH HHS R21 DK080970
6 · The paper itself

Abstract

Pathological angiogenesis is a hallmark of many diseases. Previously, we reported that orphan nuclear receptor TR3/Nur77 was a critical mediator of angiogenesis to regulate tumor growth and skin wound healing via regulating the expression of the junctional proteins and integrins. However, the molecular mechanism, by which TR3/Nur77 regulates angiogenesis is not completely understood. Here, we were the first to find that TR3/Nur77, via its various amino acid fragments, regulated the expression of DLL4 and Jagged 1 in cultured endothelial cells. DLL4 and Jagged1 mediated TR3/Nur77-induced angiogenic responses and signaling molecules, but not the expression of integrins. Instead, integrins regulated the expressions of DLL4 and Jagged1 induced by TR3/Nur77. Further, DLL4, Jagged1 and integrins α1, α2, β3 and β5 were regulated by TR3/Nur77 in animal sepsis models of lipopolysaccharide (LPS)-induced endotoxemia, and cecal ligation and puncture (CLP), in which, TR3/Nur77 expression was significantly and tranciently increased. Mouse survival rates were greatly increased in Nur77 knockout mice bearing both CLP and LPS models. The results elucidated a novel axis of VEGF/histamine ➔ TR3/Nur77 ➔ integrins ➔ DLL4/Jagged1 in angiogenesis, and demonstrated that TR3/Nur77 was an excellent target for sepsis. These studies supported our previous findings that TR3/Nur77 was an excellent therapeutic target, and further our understanding of the molecular mechanism, by which TR3/Nur77 regulated angiogenesis.

Indexed as

Neovascularization, PhysiologicAdaptor Proteins, Signal TransducingAnimalsCalcium-Binding ProteinsCells, CulturedDisease Models, AnimalEndotoxemiaFemaleHumansHuman Umbilical Vein Endothelial CellsIntegrinsIntercellular Signaling Peptides and ProteinsIntracellular Signaling Peptides and ProteinsJagged-1 ProteinMaleMembrane ProteinsAdaptor Proteins, Signal TransducingCalcium-Binding ProteinsDLL4 protein, humanDLL4 protein, mouseIntegrinsIntercellular Signaling Peptides and ProteinsIntracellular Signaling Peptides and ProteinsJAG1 protein, humanJag1 protein, mouseJagged-1 ProteinMembrane ProteinsNR4A1 protein, humanNr4a1 protein, mouseNuclear Receptor Subfamily 4, Group A, Member 1AngiogenesisDLL4IntegrinJagged1SepsisTR3/Nur77

Identifiers

PMID30930165
PMCPMC6474785
OpenAlexW2934692354

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.