Troglitazone inhibits synthesis of transforming growth factor-beta1 and reduces matrix production in human peritoneal mesothelial cells.
OBJECTIVE
Peritoneal matrix accumulation is a characteristic of peritoneal fibrosis (PF). Continuous ambulatory peritoneal dialysis (CAPD) patients with up-regulation of transforming growth factor-beta1 (TGF-beta1) in their drained effluent show an increased risk of PF. Inhibition of TGF-beta1 expression in human peritoneal mesothelial cells (HPMC) may provide a potential treatment for PF. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists are increasingly used in patients with diabetes, but their effects on extracellular matrix (ECM) turnover are unknown. The aims of this study were to investigate the effects of the PPAR-gamma agonist troglitazone on TGF-beta1 expression and matrix production in HPMC.


METHODS
Human peritoneal mesothelial cells were cultured from human omentum by an enzyme digestion method, grown in a medium containing 30 mmol/L D-glucose. TGF-beta1 expression and matrix production and turnover were measured in HPMC in the presence and absence of 15 micromol/L troglitazone. The mRNA expressions of TGF-beta(1), Collagen I (Col I) and fibronectin (FN) were determined by semiquantification reverse-transcriptive polymerase chain reaction (RT-PCR). The protein of TGF-beta1 was determined by ELISA and proteins of Col I, FN were determined by western blot.


RESULTS
The mRNA expression and protein of TGF-beta(1), Col I, FN were significantly increased in HPMC stimulated with 30 mmol/L D-glucose compared to the control group with F12 media (P < 0.01), which was reversed in the presence of troglitazone (15 micromol/L). Obvious decrease of TGF-beta(1) was found in troglitazone-treated groups as compared to groups stimulated with GS (P < 0.05). Exposure of HPMC to troglitazone reduced collagen I secretion (P < 0.05), and fibronectin secretion (P < 0.05).


CONCLUSIONS
Troglitazone reduce the expression of TGF-beta(1) in HPMC stimulated by 30 mmol/L D-glucose, and reduces ECM production. These studies suggest that the PPAR-gamma agonists may have a specific role in ameliorating the course of progressive peritoneal fibrosis under long-term peritoneal dialysis states.
Peng
Youming
Y
Department of Nephrology, Nephrology Institute of Central South University, 2nd Xiangya Hospital, Central South University, Changsha, Hunan, China.
Liu
Hong
H
Liu
Fuyou
F
Liu
Yinghong
Y
Li
Jun
J
Chen
Xing
X
D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007150:Immunohistochemistry; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D010537:Peritoneum / Q000166:cytology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D000077288:Troglitazone
D002839:Chromans; D024042:Collagen Type I; D005353:Fibronectins; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D053773:Transforming Growth Factor beta1; D000077288:Troglitazone; D005947:Glucose