Irisin restores high glucose-induced cell injury in vascular endothelial cells by activating Notch pathway via Notch receptor 1

Biosci Biotechnol Biochem. 2021 Sep 22;85(10):2093-2102. doi: 10.1093/bbb/zbab137.

Abstract

Diabetic foot ulcers (DFU) are a vascular complication of diabetes mellitus (DM). It has been confirmed that irisin is closely related to DM. However, the effect of irisin on DFU is obscure and needs further study. After human umbilical vein endothelial cell lines (HUVECs) were treated with different concentrations' irisin, normal glucose, high glucose (HG), HG plus irisin-high (H) or sh-Notch1, cell biological behaviors, LDH, and VEGFA were detected by cell function experiments. Apoptosis- and Notch pathway-related protein levels were evaluated by Western blot. Irisin has no cytotoxicity, and irisin-H elevated cell viability and inhibited apoptosis and LDH level in HG-induced HUVECs. Meanwhile, irisin-H restored HG-repressed migration and angiogenesis in HUVECs. Irisin-H inhibited apoptosis-related protein levels and promoted VEGFA and Notch pathway-related protein levels in HG-treated HUVECs. Additionally, sh-Notch1 reversed the protective effect of irisin-H in HG-treated HUVECs. Irisin restores HG-induced cell injury and angiogenesis in HUVECs by activating Notch pathway via Notch1.

Keywords: Notch; angiogenesis; human umbilical vein endothelial cells; irisin.

MeSH terms

  • Apoptosis
  • Cell Survival
  • Human Umbilical Vein Endothelial Cells*
  • Humans
  • Proto-Oncogene Proteins c-akt

Substances

  • Proto-Oncogene Proteins c-akt