Influence of glucose and inflammatory cytokines on TGF-beta1 and CTGF mRNA expressions in human peritoneal mesothelial cells.
Peritoneal fibrosis is a major complication of long-term continuous ambulatory peritoneal dialysis (CAPD) treatment. Transforming growth factor-beta (TGF-beta) 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-beta 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-beta1 and CTGF mRNA were quantified by one step real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). TGF-beta1 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-beta1 and CTGF. Effects of inflammatory cytokines were also examined by adding tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) or interleukin-6 (IL-6) to the medium at 0.1 ng/ml for 2 days. TGF-beta1 expression tended to be increased by TNF-alpha and IL-6. On the other hand, CTGF expression was significantly decreased (p<0.01) by IL-1 but not changed by TNF-alpha or IL-6. These results suggest that high glucose concentration may play a central role in peritoneal fibrosis. Responses of TGF-beta1 and CTGF to inflammatory cytokines were not necessarily identical, suggesting that CTGF may be a better therapeutic target for peritoneal fibrosis than TGF-beta1.
Sakamoto
Nobuyoshi
N
Department of Urology, Osaka City University Graduate School of Medicine, Asahi-machi, Osaka 545-8585, Japan.
Sugimura
Kazunobu
K
Kawashima
Hidenori
H
Tsuchida
Kenji
K
Takemoto
Yoshiaki
Y
Naganuma
Toshihide
T
Tatsumi
Shinji
S
Nakatani
Tatsuya
T
D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D009852:Omentum / Q000166:cytology; D010537:Peritoneum / Q000166:cytology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C526317:CCN2 protein, human; D016207:Cytokines; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D055513:Connective Tissue Growth Factor; D005947:Glucose