Evidence map›Paper›PMID 28288111›Full record

ArticleNature medicine2017

Gpr124 is essential for blood-brain barrier integrity in central nervous system disease.

Junlei Chang, Michael R Mancuso, Carolina Maier, Xibin Liang, Kanako Yuki, Lu Yang, Jeffrey W Kwong, Jing Wang, Varsha Rao, Mario Vallon and 24 more

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05585255 (Clinical Significance, Mechanism of Action, and New Targeted Drug Research of DKK2 Protein in Cerebral Ischemia-reperfusion Injury), which is not on this map. Cited by 158 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
158citing papers in PubMed, 1 pooled it
9.8field-weighted citation impact, top 1% 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.

NCT05585255 unknown statusnot on this mapstarted 2022, after this paper: background citation

Clinical Significance, Mechanism of Action, and New Targeted Drug Research of DKK2 Protein in Cerebral Ischemia-reperfusion Injury

Typeobservational_patient_registrySponsorNanfang Hospital, Southern Medical UniversityRan2022 to 2024Enrolled108ConditionsIschemic Stroke, Acute, Ischemia-reperfusion Injury, Cerebral EdemaArmsenzyme-linked immunosorbent assay(ELISA)
3 · Its place in the literature

Who cites it

158 citing papers in PubMed, 1 synthesis or guideline pooled it, 254 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Cell-to-Cell Signaling Networks at the Blood-Brain Barrier in Health and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Adhesion G protein-coupled receptors.Pharmacological reviews · 2026
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
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98 more citing papers are in PubMed but not listed here.

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

34 authors at 2 institutions in 1 country.

Junlei ChangDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Michael R MancusoDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Carolina MaierDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA.
Xibin LiangDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Kanako YukiDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Lu YangDepartment of Molecular and Cellular Biology and Integrative Genomics Core, City of Hope, Duarte, California, USA.
Jeffrey W KwongDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Jing WangDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Varsha RaoDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Mario VallonDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Cynthia KosinskiDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
J J Haijing ZhangDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Amanda T MahDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Lijun XuDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California, USA.
Le LiDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California, USA.
Sharareh GholaminDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA.
Teresa F ReyesDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Rui LiDepartment of Dermatology, Stanford University School of Medicine, Stanford, California, USA.
Frank KuhnertDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Xiaoyuan HanDepartment of Urology, Stanford University School of Medicine, Stanford, California, USA.
Jenny YuanDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Shin-Heng ChiouDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Ari D BrettmanDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Lauren DalyDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
David C CorneyDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Samuel H CheshierDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA.
Linda D ShortliffeDepartment of Urology, Stanford University School of Medicine, Stanford, California, USA.
Xiwei WuDepartment of Molecular and Cellular Biology and Integrative Genomics Core, City of Hope, Duarte, California, USA.
Michael SnyderDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Pak ChanDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA.
Rona G GiffardDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California, USA.
Howard Y ChangDepartment of Dermatology, Stanford University School of Medicine, Stanford, California, USA.
Katrin AndreassonDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Calvin J KuoDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Stanford University · USCity of Hope · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
Special EquipmentP50HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2014 to 2018
$15.2M
Regulation of actively proliferating and quiescent intestinal stem cellsU01DK085527 · NIDDK · STANFORD UNIVERSITY · PI KUO, CALVIN J · 2009 to 2023
$6.9M
Intestinal Stem Cell Consortium Coordinating CenterU01DK085532 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NILAND, JOYCE CAROL · 2009 to 2018
$6.5M
Limited Competition for the Continuation of the Intestinal Stem Cell Consortium Coordinating CenterU24DK085532 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NILAND, JOYCE CAROL · 2019 to 2023
$2.3M
VEGF Regulation of Hepatic Erythropoietin SynthesisR01HL074267 · NHLBI · STANFORD UNIVERSITY · PI KUO, CALVIN J · 2005 to 2009
$1.9M
miR-126 Regulation of Tumor ProgressionR01CA158528 · NCI · STANFORD UNIVERSITY · PI KUO, CALVIN J · 2011 to 2015
$1.9M
Regulation of Adult CNS Angiogenesis by GPR124R01NS064517 · NINDS · STANFORD UNIVERSITY · PI KUO, CALVIN J · 2010 to 2014
$1.8M
Four Laser, 18 Color Cell Sorter in the SSFFS10RR025518 · NCRR · STANFORD UNIVERSITY · PI HERZENBERG, LEONARD A · 2009 to 2009
$500k
BD Canto II RUO CytometerS10RR027431 · NCRR · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2010 to 2010
$236k
NCI NIH HHS P30 CA033572NCI NIH HHS R01 CA158528NCRR NIH HHS S10 RR025518NCRR NIH HHS S10 RR027431NHGRI NIH HHS P50 HG007735NHLBI NIH HHS R01 HL074267NIDDK NIH HHS U01 DK085527NIDDK NIH HHS U01 DK085532NIDDK NIH HHS U24 DK085532NIGMS NIH HHS T32 GM007365NINDS NIH HHS R01 NS064517
6 · The paper itself

Abstract

Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt-β-catenin signaling. Constitutive activation of Wnt-β-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124-CKO mice, with rescue of the endothelial gene tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption.

Indexed as

AnimalsBlood-Brain BarrierDisease Models, AnimalEndothelial CellsExtracellular MatrixFlow CytometryFluorescent Antibody TechniqueGlioblastomaInfarction, Middle Cerebral ArteryIntracranial HemorrhagesMiceMice, KnockoutMicroscopy, ElectronMicrovesselsPericytesReal-Time Polymerase Chain ReactionGPR124 protein, mouseReceptors, G-Protein-Coupled

Identifiers

PMID28288111
PMCPMC5559385
OpenAlexW2595618349

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Registered trials

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.