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

来源：

TOXICOLOGY LETTERS | 2009年 / 187卷 / 01期

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

页码：22 / 27

页数：6

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