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Troglitazone inhibits synthesis of transforming growth factor-beta1 and reduces matrix production in human peritoneal mesothelial cells.
Nephrology (Carlton). 2006 Dec; 11(6):516-23.N

Abstract

AIM

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).

CONCLUSION

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.

Authors+Show Affiliations

Department of Nephrology, Nephrology Institute of Central South University, 2nd Xiangya Hospital, Central South University, Changsha, Hunan, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17199790

Citation

Peng, Youming, et al. "Troglitazone Inhibits Synthesis of Transforming Growth Factor-beta1 and Reduces Matrix Production in Human Peritoneal Mesothelial Cells." Nephrology (Carlton, Vic.), vol. 11, no. 6, 2006, pp. 516-23.
Peng Y, Liu H, Liu F, et al. Troglitazone inhibits synthesis of transforming growth factor-beta1 and reduces matrix production in human peritoneal mesothelial cells. Nephrology (Carlton). 2006;11(6):516-23.
Peng, Y., Liu, H., Liu, F., Liu, Y., Li, J., & Chen, X. (2006). Troglitazone inhibits synthesis of transforming growth factor-beta1 and reduces matrix production in human peritoneal mesothelial cells. Nephrology (Carlton, Vic.), 11(6), 516-23.
Peng Y, et al. Troglitazone Inhibits Synthesis of Transforming Growth Factor-beta1 and Reduces Matrix Production in Human Peritoneal Mesothelial Cells. Nephrology (Carlton). 2006;11(6):516-23. PubMed PMID: 17199790.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Troglitazone inhibits synthesis of transforming growth factor-beta1 and reduces matrix production in human peritoneal mesothelial cells. AU - Peng,Youming, AU - Liu,Hong, AU - Liu,Fuyou, AU - Liu,Yinghong, AU - Li,Jun, AU - Chen,Xing, PY - 2007/1/4/pubmed PY - 2007/3/28/medline PY - 2007/1/4/entrez SP - 516 EP - 23 JF - Nephrology (Carlton, Vic.) JO - Nephrology (Carlton) VL - 11 IS - 6 N2 - AIM: 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). CONCLUSION: 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. SN - 1320-5358 UR - https://www.unboundmedicine.com/medline/citation/17199790/Troglitazone_inhibits_synthesis_of_transforming_growth_factor_beta1_and_reduces_matrix_production_in_human_peritoneal_mesothelial_cells_ L2 - https://doi.org/10.1111/j.1440-1797.2006.00654.x DB - PRIME DP - Unbound Medicine ER -