Author:
Arjunan Pachiappan,Lin Xianchai,Tang Zhongshu,Du Yuxiang,Kumar Anil,Liu Lixian,Yin Xiangke,Huang Lijuan,Chen Wei,Chen Qishan,Ye Zhimin,Wang Shasha,Kuang Haiqing,Zhou Linbin,Xu Kai,Chen Xue,Zeng Haitao,Lu Weisi,Cao Yihai,Liu Yizhi,Zhao Chen,Li Xuri
Abstract
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 up-regulates 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.
Funder
National Natural Science Foundation of China
Publisher
Proceedings of the National Academy of Sciences
Cited by
44 articles.
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