1. Academic Validation
  2. GBP2 inhibits pathological angiogenesis in the retina via the AKT/mTOR/VEGFA axis

GBP2 inhibits pathological angiogenesis in the retina via the AKT/mTOR/VEGFA axis

  • Microvasc Res. 2024 Apr 16:154:104689. doi: 10.1016/j.mvr.2024.104689.
Xiaoxiang Xu 1 Xihui Ding 1 Zizhuo Wang 1 Shujiang Ye 2 Jianguang Xu 3 Zugang Liang 4 Renfei Luo 1 Jinyong Xu 1 Xiaohui Li 5 Zhenhua Ren 6
Affiliations

Affiliations

  • 1 Department of Anatomy, Anhui Medical University, Hefei, Anhui 230032, China.
  • 2 Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230012, China; Anhui Public Health Clinical Center, Hefei, Anhui 230012, China.
  • 3 College and Hospital of Stomatology, Key Lab. of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, Anhui 230032, China.
  • 4 Hefei Huaxia Mingren Eye Hospital, Hefei, Anhui 230032, China.
  • 5 Department of Anatomy, Anhui Medical University, Hefei, Anhui 230032, China. Electronic address: 1292936941@qq.com.
  • 6 Department of Anatomy, Anhui Medical University, Hefei, Anhui 230032, China; College and Hospital of Stomatology, Key Lab. of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, Anhui 230032, China. Electronic address: renzhenhua1975@163.com.
Abstract

Pathological retinal angiogenesis is not only the hallmark of retinopathies, but also a major cause of blindness. Guanylate binding protein 2 (GBP2) has been reported to be associated with retinal diseases such as diabetic retinopathy and hypoxic retinopathy. However, GBP2-mediated pathological retinal angiogenesis remains largely unknown. The present study aimed to investigate the role of GBP2 in pathological retinal angiogenesis and its underlying molecular mechanism. In this study, we established oxygen-induced retinopathy (OIR) mice model for in vivo study and hypoxia-induced angiogenesis in ARPE-19 cells for in vitro study. We demonstrated that GBP2 expression was markedly downregulated in the retina of mice with OIR and ARPE-19 cells treated with hypoxia, which was associated with pathological retinal angiogenesis. The regulatory mechanism of GBP2 in ARPE-19 cells was studied by GBP2 silencing and overexpression. The regulatory mechanism of GBP2 in the retina was investigated by overexpressing GBP2 in the retina of OIR mice. Mechanistically, GBP2 downregulated the expression and secretion of vascular endothelial growth factor (VEGFA) in ARPE-19 cells and retina of OIR mice. Interestingly, overexpression of GBP2 significantly inhibited neovascularization in OIR mice, conditioned medium of GBP2 overexpressing ARPE-19 cells inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, we confirmed that GBP2 downregulated VEGFA expression and angiogenesis by inhibiting the Akt/mTOR signaling pathway. Taken together, we concluded that GBP2 inhibited pathological retinal angiogenesis via the Akt/mTOR/VEGFA axis, thereby suggesting that GBP2 may be a therapeutic target for pathological retinal angiogenesis.

Keywords

Guanylate-binding protein 2; Pathologic angiogenesis; Retinal neovascularization; Vascular endothelial growth factor.

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