Evidence map›Paper›PMID 28928465›Full record

ArticleNature communications2017

Endothelial adenosine A2a receptor-mediated glycolysis is essential for pathological retinal angiogenesis.

Zhiping Liu, Siyuan Yan, Jiaojiao Wang, Yiming Xu, Yong Wang, Shuya Zhang, Xizhen Xu, Qiuhua Yang, Xianqiu Zeng, Yaqi Zhou and 20 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
7.7field-weighted citation impact, top 2% 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

78 citing papers in PubMed, 120 citations in OpenAlex.

  1. Review
  2. From danger to resolution: targeting purinergic signaling in CNS diseases.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
  3. Article
  4. Article
  5. The role of lactate in retinal health and disease: mechanisms and potential therapeutic strategies. A narrative review.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
    Review
  6. Article
  7. Article
  8. Molecular stress and neurovascular injury in the diabetic retina.The Journal of clinical investigation · 2026
    Review
  9. Article
  10. Article
  11. Dual blockade of adenosine AFrontiers in immunology · 2026
    Article
  12. Article
  13. Article
  14. Article
  15. Targeting adenosine APurinergic signalling · 2025
    Review
  16. Semaphorin 6A phase separation sustains a histone lactylation-dependent lactate buildup in pathological angiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  17. Review
  18. Single-cell analysis identifies MKI67Journal of translational medicine · 2025
    Article
  19. Review
  20. Review

18 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

30 authors at 10 institutions in 2 countries.

Zhiping LiuDrug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Siyuan YanVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
Jiaojiao WangDrug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Yiming XuVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.ORCID http://orcid.org/0000-0002-9537-3664
Yong WangVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
Shuya ZhangMolecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, 325035, China.
Xizhen XuVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
Qiuhua YangDrug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Xianqiu ZengDrug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Yaqi ZhouDrug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Xuejiao GuMolecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, 325035, China.
Sarah LuVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
Zhongjie FuDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
David J FultonVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
Neal L WeintraubVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
Ruth B CaldwellVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
Wenbo ZhangDepartment of Ophthalmology & Visual Sciences, University of Texas Medical Branch (UTMB), Galveston, TX, 77555, USA.
Chaodong WuDepartment of Nutrition and Food Science, Texas A&M University, College Station, TX, 77843, USA.ORCID http://orcid.org/0000-0001-8569-8070
Xiao-Ling LiuMolecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, 325035, China.
Jiang-Fan ChenMolecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, 325035, China.
Aftab AhmadDepartment of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, 35249, USA.
Ismail Kaddour-DjebbarDepartment of Physiology, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
Mohamed Al-ShabraweyJames and Jean Culver Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
Qinkai LiDrug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Xuejun JiangState Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Science, Beijing, 100101, China.
Ye SunDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0002-7674-9056
Akrit SodhiWilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA.
Lois SmithDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Mei HongDrug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China. meihong@pkusz.edu.cn.
Yuqing HuoVascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA. yhuo@augusta.edu.
Augusta University · USPeking University · CNBoston Children's Hospital · USWenzhou Medical University · CNBoston University · USInstitute of Microbiology · CNJohns Hopkins University · USTexas A&M University · USThe University of Texas Medical Branch at Galveston · USUniversity of Alabama at Birmingham · US

Funding

Dietary control of angiogenesis in retinopathy modelsR01EY017017 · NEI · BOSTON CHILDREN'S HOSPITAL · PI Zhongjie Fu, Lois Smith · 2006 to 2026
$11.8M
Novel therapies to inhibit Diabetic RetinopathyR24EY024864 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI KERN, TIMOTHY S · 2015 to 2019
$8.1M
Mouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI WOOLF, CLIFFORD J · 2016 to 2020
$5.2M
Promotion of retinal vascular hyperpermeability and macular edema by ANGPTL4R01EY025705 · NEI · UNIVERSITY OF MARYLAND BALTIMORE · PI MONTANER, SILVIA V · 2016 to 2020
$2.6M
Role of lipoxygenase pathway in early microvascular dysfunction during diabetic rR01EY023315 · NEI · AUGUSTA UNIVERSITY · PI AL-SHABRAWEY, MOHAMED AL-SAYED · 2013 to 2017
$1.8M
Epigenetic regulation of HDAC9 in obesity and atherosclerosisR01HL126949 · NHLBI · AUGUSTA UNIVERSITY · PI WEINTRAUB, NEAL L · 2016 to 2019
$1.8M
Glucose/lipid metabolism and vessel development in phase I ROPR01EY030904 · NEI · BOSTON CHILDREN'S HOSPITAL · PI SMITH, LOIS · 2020 to 2023
$1.7M
Protective role of adenosine 2A receptor in NAFLDR01DK095862 · NIDDK · TEXAS A&M AGRILIFE RESEARCH · PI WU, CHAODONG · 2013 to 2017
$1.6M
The role of adenosine kinase in atherosclerosisR01HL095556 · NHLBI · UNIVERSITY OF MINNESOTA · PI HUO, YUQING · 2011 to 2015
$1.5M
Hypoxic factors in pulmonary hypertensionR01HL114933 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI AHMAD, AFTAB · 2014 to 2018
$1.5M
NEI NIH HHS R01 EY017017NEI NIH HHS R01 EY023315NEI NIH HHS R01 EY025705NEI NIH HHS R01 EY030904NEI NIH HHS R24 EY024864NHLBI NIH HHS R01 HL095556NHLBI NIH HHS R01 HL114933NHLBI NIH HHS R01 HL126949NICHD NIH HHS U54 HD090255NIDDK NIH HHS R01 DK095862NIH HHS HL095556NIH HHS R01DK095862
6 · The paper itself

Abstract

Adenosine/adenosine receptor-mediated signaling has been implicated in the development of various ischemic diseases, including ischemic retinopathies. Here, we show that the adenosine A2a receptor (ADORA2A) promotes hypoxia-inducible transcription factor-1 (HIF-1)-dependent endothelial cell glycolysis, which is crucial for pathological angiogenesis in proliferative retinopathies. Adora2a expression is markedly increased in the retina of mice with oxygen-induced retinopathy (OIR). Endothelial cell-specific, but not macrophage-specific Adora2a deletion decreases key glycolytic enzymes and reduces pathological neovascularization in the OIR mice. In human primary retinal microvascular endothelial cells, hypoxia induces the expression of ADORA2A by activating HIF-2α. ADORA2A knockdown decreases hypoxia-induced glycolytic enzyme expression, glycolytic flux, and endothelial cell proliferation, sprouting and tubule formation. Mechanistically, ADORA2A activation promotes the transcriptional induction of glycolytic enzymes via ERK- and Akt-dependent translational activation of HIF-1α protein. Taken together, these findings advance translation of ADORA2A as a therapeutic target in the treatment of proliferative retinopathies and other diseases dependent on pathological angiogenesis.Pathological angiogenesis in the retina is a major cause of blindness. Here the authors show that adenosine receptor A2A drives pathological angiogenesis in the oxygen-induced retinopathy mouse model by promoting glycolysis in endothelial cells via the ERK/Akt/HIF-1α pathway, thereby suggesting new therapeutic targets for disease treatment.

Indexed as

AnimalsDisease Models, AnimalEndothelial CellsFemaleGlycolysisHumansHypoxia-Inducible Factor 1, alpha SubunitMaleMiceMice, Inbred C57BLMice, KnockoutReceptor, Adenosine A2ARetinaRetinal DiseasesRetinal NeovascularizationHypoxia-Inducible Factor 1, alpha SubunitReceptor, Adenosine A2A

Identifiers

PMID28928465
PMCPMC5605640
OpenAlexW2755476069

What OpenQuestion holds

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Read underepoch 390

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.