https://scholars.lib.ntu.edu.tw/handle/123456789/521505
標題: | Pentoxifylline modulates intracellular signalling of TGF-β in cultured human peritoneal mesothelial cells: Implications for prevention of encapsulating peritoneal sclerosis | 作者: | KUAN-YU HUNG JENQ-WEN HUANG Chen C.-T. PO-HUANG LEE TUN-JUN TSAI |
公開日期: | 2003 | 卷: | 18 | 期: | 4 | 起(迄)頁: | 670-676 | 來源出版物: | Nephrology Dialysis Transplantation | 摘要: | 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-β 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-β signalling. However, how PTX modulates the intracellular signalling downstream to TGF-β 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-β-induced collagen gene expression in HPMC. Methods. HPMC was cultured from human omentum by an enzyme digestion method. The expression of collagen α1(I) mRNA was determined by northern blotting, while the SMAD proteins and the MAPK kinase activity were determined by western blotting. Results. TGF-β-stimulated collagen α1(I) mRNA expression of HPMC was inhibited by PTX. The Smad2, ERK1/2 and p38HOG pathways were activated in response to TGF-β. However, TGF-β 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-β-induced collagen α1(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-β. In contrast, PTX had no effect on the TGF-β-induced activation of Smad2, under the same concentration. Conclusion. PTX inhibits the TGF-β-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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-0037385709&doi=10.1093%2fndt%2fgfg141&partnerID=40&md5=00061ec3cfff059282c4dedd50e338db https://scholars.lib.ntu.edu.tw/handle/123456789/521505 |
ISSN: | 0931-0509 | DOI: | 10.1093/ndt/gfg141 | SDG/關鍵字: | 2 (2 amino 3 methoxyphenyl)chromone; 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole; collagen; collagen type 1; Janus kinase; messenger RNA; mitogen activated protein kinase; mitogen activated protein kinase 1; n [2 (4 bromocinnamylamino)ethyl] 5 isoquinolinesulfonamide; pentoxifylline; protein inhibitor; Smad protein; Smad2 protein; synaptophysin; transforming growth factor beta; article; cell culture; cell stimulation; clinical feature; concentration response; controlled study; culture technique; drug effect; encapsulating peritoneal sclerosis; enzyme activation; enzyme activity; enzyme degradation; gene expression; human; human cell; human tissue; long term care; mesothelium cell; Northern blotting; omentum; peritoneal dialysis; peritoneum cell; priority journal; protein expression; protein family; sclerosis; signal transduction; Western blotting; Blotting, Northern; Blotting, Western; Cells, Cultured; Epithelial Cells; Humans; Pentoxifylline; Peritoneal Cavity; Peritoneal Diseases; Peritoneum; Probability; RNA, Messenger; Sclerosis; Sensitivity and Specificity; Signal Transduction; Trans-Activators; Transforming Growth Factor beta |
顯示於: | 醫學系 |
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