Involvement of multiple scavenger receptors in advanced glycation end product-induced vessel tube formation in endothelial cells

Yui Yamazaki, Hidenori Wake, Takashi Nishinaka, Omer Faruk Hatipoglu, Keyue Liu, Masahiro Watanabe, Takao Toyomura, Shuji Mori, Tadashi Yoshino, Masahiro Nishibori, Hideo Takahashi

Research output: Contribution to journalArticlepeer-review

Abstract

Toxic advanced glycation end products (toxic AGEs) derived from glycolaldehyde (AGE3) have been implicated in the development of diabetic vascular complications such as retinopathy characterised by excessive angiogenesis. Different receptor types, such as receptor for AGEs (RAGE), Toll like receptor-4 and scavenger receptors, are expressed in endothelial cells and contribute to AGE-elicited alteration of cell function. In the present study, we examined the involvement of AGE-related receptors on AGE-induced angiogenesis in endothelial cells. The effects of pharmacological inhibitors or receptor neutralizing antibodies on AGE3-induced tube formation were investigated using the in vitro Matrigel tube formation assay in b.End5 cells (mouse endothelial cells). AGE3-induced signalling pathways and receptor expression changes were analysed by Western blot analysis and flow cytometry, respectively. Both FPS-ZM1, a RAGE inhibitor, and fucoidan, a ligand for scavenger receptors, suppressed AGE3-induced tube formation. Cocktails of neutralizing antibodies against the scavenger receptors CD36, CD163 and LOX-1 prevented AGE3-induced tube formation. AGE3 activated mTOR signalling, resulting in facilitation of tube formation. Activation of the AGE-RAGE pathway also led to the upregulation of scavenger receptors. Taken together, our findings suggest that the scavenger receptors CD36, CD163 and LOX-1 in conjunction with the RAGE receptor work together to mediate toxic AGE-induced facilitation of angiogenesis.

Original languageEnglish
Article number112857
JournalExperimental Cell Research
Volume408
Issue number1
DOIs
Publication statusPublished - Nov 1 2021
Externally publishedYes

Keywords

  • AGEs
  • Angiogenesis
  • Endothelial cell
  • RAGE
  • Scavenger receptor
  • mTOR

ASJC Scopus subject areas

  • Cell Biology

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