Damage to the Peritoneal Membrane by Glucose Degradation Products Is Mediated by the Receptor for Advanced Glycation End-Products
Open Access
- 1 January 2006
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 17 (1), 199-207
- https://doi.org/10.1681/asn.2005020155
Abstract
Peritoneal dialysis is limited by morphologic changes of the peritoneal membrane. Use of peritoneal dialysis fluids (PDF) that contain glucose degradation products (GDP) generates advanced glycation end-products (AGE) within the peritoneal cavity. It is unknown whether peritoneal damage is causally related to AGE–receptor for AGE (RAGE) interaction. The effects of PDF were compared with different amounts of GDP on morphologic changes of the peritoneal membrane in 48 wild-type (WT) and 48 RAGE-deficient mice. PDF (1 ml) were instilled twice daily over a period of 12 wk. Groups with eight animals each received no manipulation (sham); sham instillation (sham i.p.); or filter-sterilized, glucose-free, conventional low GDP- or high GDP PDF. In vitro (generation of AGE fluorescence in PDF) and in vivo (immunohistochemistry for carboxymethyllysine), a GDP-dependent increase of AGE formation occurred. Inflammation and neoangiogenesis were augmented in WT mice that were treated with high GDP accompanied by upregulation of CD3+ T cells, increased NF-κB binding activity, increased lectin, and vascular endothelial growth factor expression. Furthermore, pronounced submesothelial fibrosis was found with increased expression of TGF-β1. Exposure to low GDP resulted in only mild inflammation and neoangiogenesis (compared with sham i.p.) and no fibrosis in WT mice. The findings in WT contrasted with those in RAGE-deficient mice, which showed no increased inflammation (CD3+ T cells and NF-κB binding activity), neoangiogenesis (by lectin and vascular endothelial growth factor expression), or fibrosis (expression of TGF-β1) after long-term exposure to GDP-containing PDF. Peritoneal damage by GDP in PDF is dependent at least in part on AGE–RAGE interaction.Keywords
This publication has 34 references indexed in Scilit:
- Advanced Glycation End Product Receptor‐Mediated Cellular DysfunctionAnnals of the New York Academy of Sciences, 2005
- Long-term exposure to new peritoneal dialysis solutions: Effects on the peritoneal membraneKidney International, 2004
- Glucose degradation products in PD fluids: Do they disappear from the peritoneal cavity and enter the systemic circulation?Kidney International, 2003
- Advanced Glycation End Products Activate Endothelium Through Signal-Transduction Receptor RAGECirculation, 2002
- Vascular endothelial growth factor production and regulation in human peritoneal mesothelial cellsKidney International, 2002
- AGEs bind to mesothelial cells via RAGE and stimulate VCAM-1 expressionKidney International, 2002
- Biochemistry and molecular cell biology of diabetic complicationsNature, 2001
- High glucose–induced PKC activation mediates TGF-β1 and fibronectin synthesis by peritoneal mesothelial cellsKidney International, 2001
- In Vitro Formation of Nϵ-(Carboxymethyl)lysine and Imidazolones under Conditions Similar to Continuous Ambulatory Peritoneal DialysisBiochemical and Biophysical Research Communications, 2001
- Advanced glycation end products increase retinal vascular endothelial growth factor expression.JCI Insight, 1998