Peritoneal fibrosis is a major complication of long-term continuous ambulatory peritoneal dialysis (CAPD) treatment. Transforming growth factor-β (TGF-β) has been reported to play an important role in the fibrosis of various tissues by stimulating connective tissue growth factor (CTGF) expression. In order to elucidate the mechanism of CAPD-related peritoneal fibrosis, we studied the influence of high glucose concentrations and inflammatory cytokines on mRNA expressions of TGF-β and CTGF in cultured human peritoneal mesothelial cells (HPMC). HPMC were isolated from normal omentum and cultured with 0.5 or 1.0% glucose or mannitol for 7 days. TGF-β1 and CTGF mRNA were quantified by one step real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). TGF-β1 and CTGF mRNA expression levels were significantly increased (p<0.05) by glucose in a dose-dependent manner, but not by mannitol. The expression levels were correlated between TGF-β1 and CTGF. Effects of inflammatory cytokines were also examined by adding tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) or interleukin-6 (IL-6) to the medium at 0.1 ng/ml for 2 days. TGF-β1 expression tended to be increased by TNF-α and IL-6. On the other hand, CTGF expression was significantly decreased (p<0.01) by IL-1 but not changed by TNF-α or IL-6. These results suggest that high glucose concentration may play a central role in peritoneal fibrosis. Responses of TGF-β1 and CTGF to inflammatory cytokines were not necessarily identical, suggesting that CTGF may be a better therapeutic target for peritoneal fibrosis than TGF-β1.

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