Effects of glucose degradation products on human peritoneal mesothelial cells

Jae Sook Song, Kyunglim Lee, Hunjoo Ha

Research output: Contribution to journalArticlepeer-review

Abstract

Both high glucose and glucose degradation products (GDP) have been implicated in alterations of peritoneal membrane structure and function during long-term peritoneal dialysis (PD). The present study examined the role of GDP including methylglyoxal (MGO), acetaldehyde, and 3,4-dideoxyglucosone (3,4-DGE) in HPMC activation with respect to membrane hyperpermeability or fibrosis. The role of reactive oxygen species (ROS) and activation of protein kinase C (PKC) in GDP-induced HPMC activation were also examined. Using M199 culture medium as control, growth arrested and synchronized HPMC were continuously stimulated by MGO, acetaldehyde, and 3,4-DGE for 48 hours. Vascular endothelial growth factor (VEGF) was quantified as a marker of peritoneal membrane hyperpermeability and fibronectin and heat shock protein 47 (hsp47) as markers of fibrosis. Involvement of ROS and PKC was examined by the inhibitory effect of N-acetylcystein (NAC) or calphostin C, respectively. MGO significantly increased VEGF (1.9-fold), Cfibronectin (1.5-fold), and hsp47 (1.3-fold) secretion compared with control M199. NAC and calphostin C effectively inhibited MGO-induced VEGF upregulation. Acetaldehyde stimulated and 3,4-DGE inhibited VEGF secretion. Fibronectin secretion and hsp47 expression in HPMC were not affected by acetaldehyde or 3,4-DGE. In conclusion, MGO upregulated VEGF and fibronectin secretion and hsp47 expression in HPMC, and PKC as well as ROS mediate MGO-induced VEGF secretion by HPMC. This implies that PKC activation and ROS generation by GDP may constitute important signals for activation of HPMC leading to progressive membrane hyperpermeability and accumulation of extracellular matrix and eventual peritoneal fibrosis.

Original languageEnglish
Pages (from-to)308-314
Number of pages7
JournalKorean Journal of Microbiology and Biotechnology
Volume33
Issue number4
StatePublished - Dec 2005

Keywords

  • Fibronectin
  • Glucose degradation products
  • Heat shock protein 47
  • Human peritoneal mesothelial cells
  • Protein kinase C
  • Reactive oxygen species
  • Vascular endothelial growth factor

Fingerprint

Dive into the research topics of 'Effects of glucose degradation products on human peritoneal mesothelial cells'. Together they form a unique fingerprint.

Cite this