OBJECTIVE: Excessive synthesis and deposition of matrix proteins by peritoneal mesothelial cells can lead to structural and functional changes in the peritoneal membrane, jeopardizing the long-term efficacy of peritoneal dialysis (PD). Prolonged exposure to high glucose concentrations in PD fluid has been implicated as a major stimulus to matrix accumulation, through the induction of transforming growth factor beta1 (TGFbeta1). This study investigated the effect of emodin (3-methyl-1,6,8-trihydroxyanthraquinone) on TGFbeta1 and fibronectin (FN) synthesis in human peritoneal mesothelial cells (HPMCs) under high glucose concentration. DESIGN: The HPMCs were preconditioned in either 5 mmol/L or 30 mmol/L D-glucose for 2 weeks prior to the addition of emodin. Cell viability was assessed by MTT assay and lactate dehydrogenase (LDH) release. Morphology of HPMCs was studied by phase-contrast microscopy. Modulation of TGFbeta1 and FN synthesis at transcription and translation were investigated by reverse transcriptase polymerase chain reaction (RT-PCR), ELISA, and Western blot analysis. RESULTS: When cultured under 30 mmol/L D-glucose, HPMCs demonstrated increased cell volume, multinucleation, and denudation of the monolayer, as compared with cells cultured under a physiologic (5 mmol/L) glucose concentration. High glucose concentration induced TGFbeta1 synthesis by HPMCs (217.17 +/- 14.88 pg/mL at 5 mmol/L D-glucose vs 370.33 +/- 20.67 pg/mL at 30 mmol/L D-glucose, p < 0.0001), and FN synthesis was induced at transcription and translation. Mannitol at 30 mmol/L did not affect HPMC morphology; matrix synthesis was also unaltered. Administration of emodin together with 30 mmol/L D-glucose resulted in amelioration of cell enlargement and exfoliation, and abrogation of TGFbeta1 induction (370.33 +/- 20.67 pg/mL for 30 mmol/L D-glucose alone vs 260.50 +/- 17.89 pg/mL for 30 mmol/L D-glucose + emodin, p < 0.0001). Synthesis of FN induced by high glucose was also reduced by 40% in the presence of emodin. CONCLUSIONS: These findings provide the first evidence that emodin can ameliorate high glucose-induced matrix synthesis in HPMCs by suppression of TGFbeta1. Emodin may thus be useful in preserving peritoneal integrity in PD.

This article has been cited by other articles:

				S. Yung, X.-R. Chen, R. C. Tsang, Q. Zhang, and T. M. Chan Reduction of Perlecan Synthesis and Induction of TGF-{beta}1 in Human Peritoneal Mesothelial Cells Due to High Dialysate Glucose Concentration: Implication in Peritoneal Dialysis J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1178 - 1188. [Abstract] [Full Text] [PDF]

				A. S. De Vriese, A. Flyvbjerg, S. Mortier, R. G. Tilton, and N. H. Lameire Inhibition of the Interaction of AGE-RAGE Prevents Hyperglycemia-Induced Fibrosis of the Peritoneal Membrane J. Am. Soc. Nephrol., August 1, 2003; 14(8): 2109 - 2118. [Abstract] [Full Text] [PDF]

Copyright © 2001 by Multimed Inc.