15-Deoxy-Δ12,14-prostaglandin J2 inhibits fibrogenic response in human hepatoma cells

被引:23
作者
Suk, Fat-Moon [2 ,3 ]
Chen, Chien-Ho [1 ]
Lin, Shyr-Yi [4 ]
Cheng, Ching-Ju [1 ]
Yen, Shish-Jung [5 ]
Hung, Ling-Fang [1 ]
Liu, Der-Zen [6 ,7 ,8 ]
Liang, Yu-Chih [1 ,8 ]
机构
[1] Taipei Med Univ, Sch Med Lab Sci & Biotechnol, Coll Med, Taipei 11014, Taiwan
[2] Taipei Med Univ Hosp, Dept Internal Med, Taipei, Taiwan
[3] Wan Fang Hosp, Taipei, Taiwan
[4] Taipei Med Univ Hosp, Dept Primary Care Med, Taipei, Taiwan
[5] Taipei City Hosp, Yang Ming Branch, Dept Lab Med, Taipei, Taiwan
[6] Taipei Med Univ, Coll Oral Med, Grad Inst Biomed Mat, Taipei 11014, Taiwan
[7] Taipei Med Univ, Coll Oral Med, Grad Inst Engn, Taipei 11014, Taiwan
[8] Taipei Med Univ Hosp, Tradit Herbal Med Res Ctr, Taipei, Taiwan
关键词
15-Deoxy-Delta(12,14)-prostaglandin J(2); TGF-beta; CTGF; Fibrosis; Hepatoma; TISSUE GROWTH-FACTOR; PROLIFERATOR-ACTIVATED-RECEPTOR; TGF-BETA; PEROXISOME-PROLIFERATOR; FACTOR EXPRESSION; LIVER FIBROSIS; STELLATE CELLS; PPAR-GAMMA; SIGNALING PATHWAYS; FACTOR CTGF/CCN2;
D O I
10.1016/j.toxlet.2009.01.019
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 [卫生毒理学];
摘要
Liver fibrosis can be induced by environmental chemicals or toxicants, and finally stimulates fibrogenic cytokines expression, such as transforming growth factor-beta(TCF-beta) and its downstream mediator connective tissue growth factor (CTGF). 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a metabolite of arachidonic acid, can act as a peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand, and function as either anti-inflammatory or inflammatory agents in different cell types. In this study, CTGF was detected in three human hepatoma cell lines, Hep3B, HepG2, and Huh-7, and it was up-regulated by TGF-beta. 15d-PGJ(2) significantly inhibited TGF-beta-induced CTGF protein and mRNA expressions, and promoter activity in hepatoma cells. 15d-PGJ2 suppressed TGF-beta-induced Smad2 phosphorylation, however enhancing the phosphorylation of ERK, c-Jun N-terminal kinase (JNK), and p38 in TGF-beta-treated Hep3B cells. Other PPAR ligands like the PPAR gamma agonist, troglitazone; the PPAR alpha agonist, Wy-14643, and bezafibrate were also able to inhibit TGF-beta-induced CTGF. The results suggest that 15d-PGJ2 inhibits TGF-beta-induced CTGF expression by inhibiting the phosphorylation of Smad2, which is independent of PPAR, and 15d-PGJ2 might also act through a PPAR-dependent mechanism in human hepatoma cells. 15d-PGJ2 might have a beneficent effect on prevention of liver fibrosis induced by environmental toxicants. (c) 2009 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:22 / 27
页数:6
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