VEGF-B is a potent antioxidant

Pachiappan Arjunan, Xianchai Lin, Zhongshu Tang, Yuxiang Du, Anil Kumar, Lixian Liu, Xiangke Yin, Lijuan Huang, Wei Chen, Qishan Chen, Zhimin Ye, Shasha Wang, Haiqing Kuang, Linbin Zhou, Kai Xu, Xue Chen, Haitao Zeng, Weisi Lu, Yihai Cao, Yizhi LiuChen Zhao, Xuri Li

Research output: Contribution to journalArticle

5 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)10351-10356
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number41
DOIs
StatePublished - Oct 9 2018

Keywords

  • Antioxidant
  • Gpx1
  • Oxidative stress
  • Retinal degeneration
  • VEGF-B

ASJC Scopus subject areas

  • General

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  • Cite this

    Arjunan, P., Lin, X., Tang, Z., Du, Y., Kumar, A., Liu, L., Yin, X., Huang, L., Chen, W., Chen, Q., Ye, Z., Wang, S., Kuang, H., Zhou, L., Xu, K., Chen, X., Zeng, H., Lu, W., Cao, Y., ... Li, X. (2018). VEGF-B is a potent antioxidant. Proceedings of the National Academy of Sciences of the United States of America, 115(41), 10351-10356. https://doi.org/10.1073/pnas.1801379115