Author
Listed:
- Zhiping Liu
(Peking University Shenzhen Graduate School
Augusta University)
- Siyuan Yan
(Augusta University
Institute of Microbiology, Chinese Academy of Science)
- Jiaojiao Wang
(Peking University Shenzhen Graduate School
Augusta University)
- Yiming Xu
(Augusta University)
- Yong Wang
(Augusta University)
- Shuya Zhang
(Wenzhou Medical University)
- Xizhen Xu
(Augusta University)
- Qiuhua Yang
(Peking University Shenzhen Graduate School
Augusta University)
- Xianqiu Zeng
(Peking University Shenzhen Graduate School
Augusta University)
- Yaqi Zhou
(Peking University Shenzhen Graduate School
Augusta University)
- Xuejiao Gu
(Wenzhou Medical University)
- Sarah Lu
(Augusta University)
- Zhongjie Fu
(Harvard Medical School)
- David J. Fulton
(Augusta University)
- Neal L. Weintraub
(Augusta University)
- Ruth B. Caldwell
(Augusta University)
- Wenbo Zhang
(University of Texas Medical Branch (UTMB))
- Chaodong Wu
(Texas A&M University)
- Xiao-Ling Liu
(Wenzhou Medical University)
- Jiang-Fan Chen
(Wenzhou Medical University
Boston University School of Medicine)
- Aftab Ahmad
(University of Alabama at Birmingham)
- Ismail Kaddour-Djebbar
(Augusta University)
- Mohamed Al-Shabrawey
(Augusta University)
- Qinkai Li
(Peking University Shenzhen Graduate School)
- Xuejun Jiang
(Institute of Microbiology, Chinese Academy of Science)
- Ye Sun
(Harvard Medical School)
- Akrit Sodhi
(Johns Hopkins School of Medicine)
- Lois Smith
(Harvard Medical School)
- Mei Hong
(Peking University Shenzhen Graduate School)
- Yuqing Huo
(Augusta University)
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.
Suggested Citation
Zhiping Liu & Siyuan Yan & Jiaojiao Wang & Yiming Xu & Yong Wang & Shuya Zhang & Xizhen Xu & Qiuhua Yang & Xianqiu Zeng & Yaqi Zhou & Xuejiao Gu & Sarah Lu & Zhongjie Fu & David J. Fulton & Neal L. We, 2017.
"Endothelial adenosine A2a receptor-mediated glycolysis is essential for pathological retinal angiogenesis,"
Nature Communications, Nature, vol. 8(1), pages 1-18, December.
Handle:
RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00551-2
DOI: 10.1038/s41467-017-00551-2
Download full text from publisher
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00551-2. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.