Emodin Ameliorates Glucose-Induced Morphologic Abnormalities and Synthesis of Transforming Growth Factor β1 and Fibronectin by Human Peritoneal Mesothelial Cells
Restricted accessResearch articleFirst published online December, 2001
Emodin Ameliorates Glucose-Induced Morphologic Abnormalities and Synthesis of Transforming Growth Factor β1 and Fibronectin by Human Peritoneal Mesothelial Cells
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 β1 (TGFβ 1). This study investigated the effect of emodin (3-methyl-1,6,8-trihydroxyanthraquinone) on TGFβ 1 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 TGFβ 1 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, multi-nucleation, and denudation of the monolayer, as compared with cells cultured under a physiologic (5 mmol/L) glucose concentration. High glucose concentration induced TGFβ 1 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 TGFβ 1 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 TGFβ 1. Emodin may thus be useful in preserving peritoneal integrity in PD.
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