NDT Advance Access published online on April 6, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh814
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong
* To whom correspondence should be addressed. Background. Glucose degradation products (GDPs) are formed during heat sterilization of peritoneal dialysis fluid and, to a lesser extent, during their prolonged storage. In vitro studies have demonstrated that GDPs impair functions of peritoneal mesothelial cells, including proliferation, viability and cytokine release. In the present study, we studied the acute effect of GDPs on the expression of tight junction-associated protein, zonula occludens protein 1 (ZO-1), in human peritoneal mesothelial cells (HPMC). The role of the vascular endothelial growth factor (VEGF) induced by GDPs in the expression of ZO-1 was also examined. Methods. HPMC were cultured with GDPs, including 2-furaldehyde (FurA), methylglyoxal (M-Glx) and 3,4-dideoxyglucosone-3-ene (3,4-DGE). The expression of ZO-1 and the synthesis of VEGF were examined. To define the role of VEGF on the regulation of ZO-1 expression, HPMC were cultured with GDPs in the presence or absence of neutralizing antibody to VEGF. The signal pathways involved in VEGF synthesis induced by GDPs were also characterized. Results. ZO-1 expression in HPMC was downregulated in a time- and dose-dependent manner following culture with subtoxic concentrations of GDPs (FurA, M-Glx and 3,4-DGE). All three GDPs increased VEGF synthesis in HPMC. Exogenous VEGF downregulated the expression of ZO-1 and neutralizing anti-VEGF antibody reversed the effect of GDPs on ZO-1 expression in HPMC, suggesting the action of GDPs on ZO-1 expression was mediated by VEGF. All three GDPs activated the p42/p44 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) signal transduction pathways. The GDP-induced VEGF and transforming growth factor (TGF)- Conclusions. We have demonstrated that short-term exposure to GDPs downregulates ZO-1 expression in HPMC through the generation of VEGF. Our study provides evidence that GDPs can directly induce VEGF and TGF-
Received October 14, 2004
Accepted March 8, 2005
Original Articles
Glucose degradation products downregulate ZO-1 expression in human peritoneal mesothelial cells: the role of VEGF
2 Department of Pathology, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong
3 Gambro AB, Lund, Sweden
Kar Neng Lai, E-mail: knlai{at}hkucc.hku.hk
Abstract 
synthesis in HPMC was partially reduced by either the p42/p44 MAPK inhibitor (PD98059) or the PKC inhibitor (staurosporine). More importantly, the VEGF and TGF- synthesis induced by GDPs in HPMC was completely blocked by synergistic action of both inhibitors. production in HPMC through the activation of p42/44 MAPK and PKC signal transduction pathways.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Yanai, J.-A. Ko, N. Nomi, N. Morishige, T.-i. Chikama, A. Hattori, K. Hozumi, M. Nomizu, and T. Nishida Upregulation of ZO-1 in Cultured Human Corneal Epithelial Cells by a Peptide (PHSRN) Corresponding to the Second Cell-Binding Site of Fibronectin Invest. Ophthalmol. Vis. Sci., June 1, 2009; 50(6): 2757 - 2764. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yamamoto, T. Tomo, E. Okabe, S. Namoto, K. Suzuki, and Y. Hirao Glutathione depletion as a mechanism of 3,4-dideoxyglucosone-3-ene-induced cytotoxicity in human peritoneal mesothelial cells: role in biocompatibility of peritoneal dialysis fluids Nephrol. Dial. Transplant., May 1, 2009; 24(5): 1436 - 1442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. N. Lai, S. C.W. Tang, and J. C.K. Leung MEDIATORS OF INFLAMMATION AND FIBROSIS Perit. Dial. Int., June 1, 2007; 27(Supplement_2): S65 - S71. [Abstract] [Full Text] [PDF]
|
|