期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 41, 页码 10351-10356出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1801379115
关键词
VEGF-B; antioxidant; oxidative stress; Gpx1; retinal degeneration
资金
- State Key Laboratory of Ophthalmology at the Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
- Key Program of the National Natural Science Foundation of China (NSFC) [81330021]
- NSFC [81670855, 81525006, 81730025]
- NSFC-Swedish Research Foundation International Collaboration Grant [81611130082]
- Guangdong Province Leading Expert Program grant
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.
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