Angiopoietin-related growth factor (AGF) supports adhesion, spreading, and migration of keratinocytes, fibroblasts, and endothelial cells through interaction with RGD-binding integrins

Biochem Biophys Res Commun. 2006 Aug 18;347(1):100-8. doi: 10.1016/j.bbrc.2006.06.053. Epub 2006 Jun 19.

Abstract

Angiopoietin-related growth factor (AGF) is a newly identified member of angiopoietin-related proteins (ARPs)/angiopoietin-like proteins (Angptls). AGF has been considered as a novel growth factor in accelerating cutaneous wound healing, as it is capable of stimulating keratinocytes proliferation as well as angiogenesis. But in our paper, we demonstrate that AGF stimulates keratinocytes proliferation only at high protein concentration, however, it can potently promote adhesion, spreading, and migration of keratinocytes, fibroblasts, and endothelial cells. Furthermore, we confirm that the adhesion and migration cellular events are mediated by RGD-binding integrins, most possibly the alpha(v)-containing integrins, by in vitro inhibition assays using synthetic competitive peptides. Our results strongly suggest that AGF is an integrin ligand as well as a mitogenic growth factor and theoretically participates in cutaneous wound healing in a more complex mechanism.

MeSH terms

  • Angiopoietin-Like Protein 6
  • Angiopoietin-like Proteins
  • Angiopoietins
  • Animals
  • Biological Factors / administration & dosage*
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Aggregation / drug effects
  • Cell Aggregation / physiology
  • Cell Line
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Dose-Response Relationship, Drug
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology*
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / physiology*
  • Humans
  • Integrin alpha Chains / metabolism*
  • Integrins / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / physiology*
  • Mice
  • Oligopeptides / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • ANGPTL6 protein, human
  • Angiopoietin-Like Protein 6
  • Angiopoietin-like Proteins
  • Angiopoietins
  • Biological Factors
  • Integrin alpha Chains
  • Integrins
  • Oligopeptides
  • arginyl-glycyl-aspartic acid