Nephrol Dial Transplant (2003) 18: 670-676
© 2003 European Renal Association-European Dialysis and Transplant Association
Pentoxifylline modulates intracellular signalling of TGF-ß in cultured human peritoneal mesothelial cells: implications for prevention of encapsulating peritoneal sclerosis
1 Department of Internal Medicine, Far-Eastern Memorial Hospital, Pan-Chiao, 2 Department of Internal Medicine, 3 Center for Optoelectronic Biomedicine and 4 Department of Surgery, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
Background. Peritoneal matrix accumulation is a major characteristic of encapsulating peritoneal sclerosis (EPS), which is a serious complication in long-term peritoneal dialysis (PD) patients. We reported previously that TGF-ß stimulates collagen gene expression in cultured HPMC, and is attenuated by pentoxifylline (PTX). The SMAD family and the mitogen-activated protein kinase (MAPK) (ERK1/2, JNK and p38HOG) pathways have been shown to participate in TGF-ß signalling. However, how PTX modulates the intracellular signalling downstream to TGF-ß remains undetermined in HPMC. In this study, we explored these signalling pathways in HPMC, and investigated the molecular mechanisms involved in the inhibitory effects of PTX on TGF-ß-induced collagen gene expression in HPMC.
Methods. HPMC was cultured from human omentum by an enzyme digestion method. The expression of collagen 
1(I) mRNA was determined by northern blotting, while the SMAD proteins and the MAPK kinase activity were determined by western blotting.
Results. TGF-ß-stimulated collagen 1(I) mRNA expression of HPMC was inhibited by PTX. The Smad2, ERK1/2 and p38HOG pathways were activated in response to TGF-ß. However, TGF-ß displayed no activation of the JNK pathway in HPMC. The addition of PD98059 and SB203580, which blocked the activation of ERK1/2 and p38HOG, respectively, suppressed the TGF-ß-induced collagen 1(I) mRNA expression. At a concentration (300 µg/ml) that inhibited the collagen gene expression, PTX suppressed the ERK1/2 and p38HOG activation by TGF-ß. In contrast, PTX had no effect on the TGF-ß-induced activation of Smad2, under the same concentration.
Conclusion. PTX inhibits the TGF-ß-induced collagen gene expression in HPMC through modulating the ERK1/2 and p38HOG pathways. Our study of PTX may provide the therapeutic basis for clinical applications in the prevention of EPS.
Keywords: encapsulating peritoneal sclerosis; mesothelial cell; pentoxifylline; signal transduction; TGF-ß
Correspondence and offprint requests to: Chin-Tin Chen, Center for Optoelectronic Biomedicine, National Taiwan University, Medical College, No. 1, Jen-Ai Road, 1st Section, Taipei, Taiwan, ROC. Email: ctchen{at}ha.mc.ntu.edu.tw
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Mizuno, Y. Ito, N. Hepburn, T. Mizuno, Y. Noda, Y. Yuzawa, C. L. Harris, B. P. Morgan, and S. Matsuo Zymosan, but Not Lipopolysaccharide, Triggers Severe and Progressive Peritoneal Injury Accompanied by Complement Activation in a Rat Peritonitis Model J. Immunol., July 15, 2009; 183(2): 1403 - 1412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-Y. Hung, J.-W. Huang, C.-K. Chiang, and T.-J. Tsai Preservation of peritoneal morphology and function by pentoxifylline in a rat model of peritoneal dialysis: molecular studies Nephrol. Dial. Transplant., December 1, 2008; 23(12): 3831 - 3840. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Guo, J. C.K. Leung, M. F. Lam, L. Y.Y. Chan, A. W.L. Tsang, H. Y. Lan, and K. N. Lai Smad7 Transgene Attenuates Peritoneal Fibrosis in Uremic Rats Treated with Peritoneal Dialysis J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2689 - 2703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-Y. Hung, K.-D. Wu, and T.-J. Tsai IN VITRO STUDY OF PERITONEAL FIBROSIS Perit. Dial. Int., June 1, 2007; 27(Supplement_2): S72 - S75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kaneko, C. Hamada, and Y. Tomino PERITONEAL FIBROSIS INTERVENTION Perit. Dial. Int., June 1, 2007; 27(Supplement_2): S82 - S86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Jofre, P. Rodriguez-Benitez, J. M. Lopez-Gomez, and R. Perez-Garcia Inflammatory Syndrome in Patients on Hemodialysis J. Am. Soc. Nephrol., December 1, 2006; 17(12_suppl_3): S274 - S280. [Abstract] [Full Text] [PDF]
|
|