https://scholars.lib.ntu.edu.tw/handle/123456789/572043
標題: | Diltiazem suppresses collagen synthesis and IL-1β-induced TGF-β1 production on human peritoneal mesothelial cells | 作者: | CHENG-CHUNG FANG CHUNG-JEN YEN YUNG-MING CHEN TZONG-SHINN CHU MING-TSAN LIN Yang J.-Y. TUN-JUN TSAI |
公開日期: | 2006 | 卷: | 21 | 期: | 5 | 起(迄)頁: | 1340-1347 | 來源出版物: | Nephrology Dialysis Transplantation | 摘要: | Background. After long-term treatment with continuous ambulatory peritoneal dialysis (CAPD), some patients may develop peritoneal fibrosis. Peritoneal mesothelial cells (PMCs) participate in the inflammatory reactions in the peritoneal cavity, and transforming growth factor-β1 (TGF-β1) and interleukin-1β (IL-1β) are involved in peritoneal fibrosis. Diltiazem is used frequently in patients with CAPD to treat hypertension. The objectives of this study were to examine the effects of diltiazem on collagen- and IL-1β-induced TGF-β1 production on human PMCs and the signalling pathway of diltiazem in this induction. Methods. Human PMCs were cultured from the enzymatic disaggregation of human omentum. Collagen synthesis was measured by [3H]proline incorporation into pepsin-resistant, salt-precipitated collagen. The expression of collagen I and III, and TGF-β1 mRNA was evaluated by northern blotting. The production of TGF-β1 by human PMCs was measured by immunoassay. The changes of intracellular calcium level after adding Fura-2-AM were measured by fluorescence spectrophotometry. Western blotting was used to assess mitogen-activated protein kinase (MAPK) signalling proteins. Results. We found that diltiazem (<0.2 mM) inhibited collagen I and III mRNA expression and collagen syntheses on a dose-dependent basis. Diltiazem (0.2 mM) suppressed IL-1β- (5 ng/ml) induced TGF-β1 production on human PMCs at both the protein and mRNA levels. Diltiazem (0.2 mM) also inhibited IL-1β- (5 ng/ml) induced collagen I and III mRNA expression. Intracellular calcium levels did not change after the treatment with diltiazem, IL-1β or both. The IL-1β-treated human PMCs increased phospho-JNK (stress-activated c-Jun N-terminal kinase) and phospho-p38 MAPK expression, while diltiazem could suppress this phenomenon. Conclusions. Diltiazem suppressed collagen synthesis of human PMCs and inhibited IL-1β-induced TGF-β1 production on human PMCs. This signalling transduction may be through p38 MAPK and JNK pathways instead of intracellular calcium. These results suggest diltiazem to be a potential therapeutic regimen in preventing peritoneal fibrosis and support further in vivo studies. ? 2006 Oxford University Press. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-33646181455&doi=10.1093%2fndt%2fgfk051&partnerID=40&md5=f8b8c729a2c534fea79c497069c7652c https://scholars.lib.ntu.edu.tw/handle/123456789/572043 |
ISSN: | 0931-0509 | DOI: | 10.1093/ndt/gfk051 | SDG/關鍵字: | calcium; collagen; collagen type 1; collagen type 3; diltiazem; fura 2 acetoxymethyl ester; interleukin 1beta; messenger RNA; mitogen activated protein kinase; mitogen activated protein kinase p38; pepsin A; proline; sodium chloride; stress activated protein kinase; transforming growth factor beta1; tritium; article; cell culture; collagen synthesis; concentration response; continuous ambulatory peritoneal dialysis; controlled study; cytokine production; drug mechanism; human; human cell; hypertension; immunoassay; in vivo study; inhibition kinetics; kidney failure; mesothelium cell; Northern blotting; peritoneal disease; peritoneum cell; priority journal; protein expression; signal transduction; spectrofluorometry; Western blotting; Analysis of Variance; Blotting, Northern; Blotting, Western; Cells, Cultured; Collagen; Diltiazem; Epithelial Cells; Fibrosis; Humans; Interleukin-1; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Probability; Risk Assessment; Sensitivity and Specificity; Transforming Growth Factor beta |
顯示於: | 醫學教育暨生醫倫理學科所 |
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