Inhibition of the interaction of age-rage prevents hyperglycemia-induced fibrosis of the peritoneal membrane

An S. De Vriese, Allan Flyvbjerg, Siska Mortier, Ronald Tilton, Norbert H. Lameire

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

The peritoneal membrane of long-term peritoneal dialysis patients is characterized by a loss of ultrafiltration capacity, associated morphologically with submesothelial fibrosis and neoangiogenesis. Exposure to high glucose concentrations in peritoneal dialysate and the resultant advanced glycation end-products (AGE) accumulation have been implicated in the development of these changes, but their exact pathophysiological role is unknown. We examined the effect of the interaction of AGE with one of their receptors (i.e., RAGE) on the function and structure of the peritoneum exposed to high ambient glucose concentrations. Streptozotocin-induced diabetic rats and control rats were treated during 6 wk with either neutralizing monoclonal anti-RAGE antibodies or control antibodies. The expression of RAGE was strongly enhanced in the peritoneal membrane of the diabetic animals. The diabetic peritonea were characterized by an elevated transport of small solutes, lower ultrafiltration rates, a higher vascular density, and an upregulation of endothelial nitric oxide synthase expression. These parameters were unaffected by treatment with anti-RAGE antibodies. In contrast, anti-RAGE but not control antibodies prevented upregulation of TGF-β, development of submesothelial fibrosis, and fibronectin accumulation in the peritoneum of diabetic animals. In conclusion, binding of AGE to RAGE increases the expression of TGF-β and contributes to the development of submesothelial fibrosis. Neoangiogenesis and the resultant loss of ultrafiltration capacity are mediated by different pathogenetic pathways.

Original languageEnglish (US)
Pages (from-to)2109-2118
Number of pages10
JournalJournal of the American Society of Nephrology
Volume14
Issue number8
StatePublished - Aug 1 2003

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Peritoneal Fibrosis
Rage
Advanced Glycosylation End Products
Peritoneum
Ultrafiltration
Hyperglycemia
Fibrosis
Membranes
Anti-Idiotypic Antibodies
Up-Regulation
Glucose
Antibodies
Nitric Oxide Synthase Type III
Dialysis Solutions
Peritoneal Dialysis
Streptozocin
Fibronectins
Blood Vessels
Monoclonal Antibodies
Inhibition (Psychology)

ASJC Scopus subject areas

  • Nephrology

Cite this

De Vriese, A. S., Flyvbjerg, A., Mortier, S., Tilton, R., & Lameire, N. H. (2003). Inhibition of the interaction of age-rage prevents hyperglycemia-induced fibrosis of the peritoneal membrane. Journal of the American Society of Nephrology, 14(8), 2109-2118.

Inhibition of the interaction of age-rage prevents hyperglycemia-induced fibrosis of the peritoneal membrane. / De Vriese, An S.; Flyvbjerg, Allan; Mortier, Siska; Tilton, Ronald; Lameire, Norbert H.

In: Journal of the American Society of Nephrology, Vol. 14, No. 8, 01.08.2003, p. 2109-2118.

Research output: Contribution to journalArticle

De Vriese, AS, Flyvbjerg, A, Mortier, S, Tilton, R & Lameire, NH 2003, 'Inhibition of the interaction of age-rage prevents hyperglycemia-induced fibrosis of the peritoneal membrane', Journal of the American Society of Nephrology, vol. 14, no. 8, pp. 2109-2118.
De Vriese, An S. ; Flyvbjerg, Allan ; Mortier, Siska ; Tilton, Ronald ; Lameire, Norbert H. / Inhibition of the interaction of age-rage prevents hyperglycemia-induced fibrosis of the peritoneal membrane. In: Journal of the American Society of Nephrology. 2003 ; Vol. 14, No. 8. pp. 2109-2118.
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