TY - JOUR
T1 - VEGF-B is a potent antioxidant
AU - Arjunan, Pachiappan
AU - Lin, Xianchai
AU - Tang, Zhongshu
AU - Du, Yuxiang
AU - Kumar, Anil
AU - Liu, Lixian
AU - Yin, Xiangke
AU - Huang, Lijuan
AU - Chen, Wei
AU - Chen, Qishan
AU - Ye, Zhimin
AU - Wang, Shasha
AU - Kuang, Haiqing
AU - Zhou, Linbin
AU - Xu, Kai
AU - Chen, Xue
AU - Zeng, Haitao
AU - Lu, Weisi
AU - Cao, Yihai
AU - Liu, Yizhi
AU - Zhao, Chen
AU - Li, Xuri
N1 - Funding Information:
ACKNOWLEDGMENTS. This work was supported by the State Key Laboratory of Ophthalmology at the Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China; a Key Program of the National Natural Science Foundation of China (NSFC) (81330021) (to X. Li); NSFC Grant 81670855 (to X. Li); NSFC–Swedish Research Foundation International Collaboration Grant 81611130082 (to X. Li); a Guangdong Province Leading Expert Program grant (to X. Li); and NSFC Grants 81525006 and 81730025 (to C.Z.).
Publisher Copyright:
© 2018 National Academy of Sciences. All rights reserved.
PY - 2018/10/9
Y1 - 2018/10/9
N2 - VEGF-B was discovered a long time ago. However, unlike VEGF-A, whose function has been extensively studied, the function of VEGF-B and the mechanisms involved still remain poorly understood. Notwithstanding, drugs that inhibit VEGF-B and other VEGF family members have been used to treat patients with neovascular diseases. It is therefore critical to have a better understanding of VEGF-B function and the underlying mechanisms. Here, using comprehensive methods and models, we have identified VEGF-B as a potent antioxidant. Loss of Vegf-b by gene deletion leads to retinal degeneration in mice, and treatment with VEGF-B rescues retinal cells from death in a retinitis pigmentosa model. Mechanistically, we demonstrate that VEGF-B upregulates numerous key antioxidative genes, particularly, Gpx1. Loss of Gpx1 activity largely diminished the antioxidative effect of VEGF-B, demonstrating that Gpx1 is at least one of the critical downstream effectors of VEGF-B. In addition, we found that the antioxidant function of VEGF-B is mediated mainly by VEGFR1. Given that oxidative stress is a crucial factor in numerous human diseases, VEGF-B may have therapeutic value for the treatment of such diseases.
AB - VEGF-B was discovered a long time ago. However, unlike VEGF-A, whose function has been extensively studied, the function of VEGF-B and the mechanisms involved still remain poorly understood. Notwithstanding, drugs that inhibit VEGF-B and other VEGF family members have been used to treat patients with neovascular diseases. It is therefore critical to have a better understanding of VEGF-B function and the underlying mechanisms. Here, using comprehensive methods and models, we have identified VEGF-B as a potent antioxidant. Loss of Vegf-b by gene deletion leads to retinal degeneration in mice, and treatment with VEGF-B rescues retinal cells from death in a retinitis pigmentosa model. Mechanistically, we demonstrate that VEGF-B upregulates numerous key antioxidative genes, particularly, Gpx1. Loss of Gpx1 activity largely diminished the antioxidative effect of VEGF-B, demonstrating that Gpx1 is at least one of the critical downstream effectors of VEGF-B. In addition, we found that the antioxidant function of VEGF-B is mediated mainly by VEGFR1. Given that oxidative stress is a crucial factor in numerous human diseases, VEGF-B may have therapeutic value for the treatment of such diseases.
KW - Antioxidant
KW - Gpx1
KW - Oxidative stress
KW - Retinal degeneration
KW - VEGF-B
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U2 - 10.1073/pnas.1801379115
DO - 10.1073/pnas.1801379115
M3 - Article
C2 - 30249667
AN - SCOPUS:85054715400
SN - 0027-8424
VL - 115
SP - 10351
EP - 10356
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 41
ER -
