The receptor for advanced glycation end-products enhances lung epithelial wound repair: An in vitro study

Exp Cell Res. 2020 Jun 15;391(2):112030. doi: 10.1016/j.yexcr.2020.112030. Epub 2020 Apr 21.

Abstract

Re-epithelialization of the alveolar surface is a key process of lung alveolar epithelial barrier repair after acute lung injury. The receptor for advanced glycation end-products (RAGE) pathway plays key roles in lung homeostasis, and its involvement in wound repair has been already reported in human bronchial epithelial cells. However, its effects on lung alveolar epithelial repair after injury remain unknown. We investigated whether RAGE stimulation with its ligands high-mobility group box 1 protein (HMGB1) or advanced glycation end-products (AGEs), alone or associated with RAGE inhibition using RAGE antagonist peptide, affects in vitro wound healing in human alveolar epithelial A549 cells. We further asked whether these effects could be associated with changes in cell proliferation and migration. We found that treatment of A549 cells with HMGB1 or AGEs promotes RAGE-dependent wound healing after a scratch assay. In addition, both RAGE ligands increased cell proliferation in a RAGE-dependent manner. Treatment with HMGB1 increased migration of alveolar epithelial cells at 12 h, independently of RAGE, whereas AGEs stimulated migration as measured 48 h after injury in a RAGE-dependent manner. Taken together, these results suggest that RAGE pathway is involved in lung alveolar epithelial wound repair, possibly through enhanced cell migration and proliferation.

Keywords: Cell migration; Cell proliferation; Lung epithelial injury; Receptor for advanced glycation end-products; Wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Cell Movement
  • Cell Proliferation
  • Epithelial Cells / cytology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Glycation End Products, Advanced / pharmacology*
  • HMGB1 Protein / pharmacology*
  • Humans
  • In Vitro Techniques
  • Lung / cytology*
  • Lung / drug effects
  • Lung / metabolism
  • Receptor for Advanced Glycation End Products / genetics
  • Receptor for Advanced Glycation End Products / metabolism*
  • Signal Transduction
  • Wound Healing*

Substances

  • Glycation End Products, Advanced
  • HMGB1 Protein
  • Receptor for Advanced Glycation End Products