The mechanism of EGFL7 regulating neovascularization in diabetic retinopathy through the PI3K/AKT/VEGFA pathway

Life Sci. 2024 Mar 1:340:122483. doi: 10.1016/j.lfs.2024.122483. Epub 2024 Feb 1.

Abstract

Diabetic retinopathy (DR) is a blinding disease caused by diabetes, characterized by neovascularization of the retina. The aim of this study was to investigate the roles of epidermal growth factor-like structural domain 7 (EGFL7) on human retinal vascular endothelial cells (HRECS) and retinas from rats with DR. An in vitro model of DR was established through culturing HRECS in high glucose. The in vivo model of DR was established by injecting SD rats with streptozotocin (STZ) to induce diabetes. The differences in the expressed levels of EGFL7, PI3K, AKT, P-AKT and VEGFA in high-glucose cultured cells and retinal tissues of diabetic rats were detected in compared to those in the control group. Stable EGFL7 knockdown cell lines were generated by transfecting HRECS with lentiviral vectors and the effects of EGFL7 knockdown on angiogenesis, cell migration and proliferation were investigated. The results showed that EGFL7, PI3K, P-AKT and VEGFA was increased in cells and tissues under high glucose conditions. Knockdown of EGFL7 downregulated the proliferation, migration and angiogenesis capacity of HRECS, and blocked the PI3K/AKT/VEGFA signaling pathway. Furthermore, overexpression of PI3K reversed the effects of EGFL7 inhibition. These findings provide new ideas for the treatment of neovascularisation in DR.

Keywords: Angiogenesis; Diabetic retinopathy; EGFL7; VEGFA.

MeSH terms

  • Animals
  • Calcium-Binding Proteins* / metabolism
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetic Retinopathy* / metabolism
  • EGF Family of Proteins* / metabolism
  • EGF Family of Proteins* / pharmacology
  • Endothelial Cells / metabolism
  • Endothelial Growth Factors
  • Glucose / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Neovascularization, Pathologic / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Transcription Factors / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Calcium-Binding Proteins
  • EGF Family of Proteins
  • EGFL7 protein, human
  • EGFL7 protein, rat
  • Endothelial Growth Factors
  • Glucose
  • Intercellular Signaling Peptides and Proteins
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • VEGFA protein, human