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

Fat Moon Suk, Chien Ho Chen, Shyr Yi Lin, Ching Ju Cheng, Shish Jung Yen, Ling Fang Hung, Der Zen Liu, Yu Chih Liang

研究成果: 雜誌貢獻文章同行評審

15 引文 斯高帕斯(Scopus)


Liver fibrosis can be induced by environmental chemicals or toxicants, and finally stimulates fibrogenic cytokines expression, such as transforming growth factor-β (TGF-β) and its downstream mediator connective tissue growth factor (CTGF). 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a metabolite of arachidonic acid, can act as a peroxisome proliferator-activated receptor γ (PPARγ) 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-β. 15d-PGJ2 significantly inhibited TGF-β-induced CTGF protein and mRNA expressions, and promoter activity in hepatoma cells. 15d-PGJ2 suppressed TGF-β-induced Smad2 phosphorylation, however enhancing the phosphorylation of ERK, c-Jun N-terminal kinase (JNK), and p38 in TGF-β-treated Hep3B cells. Other PPAR ligands like the PPARγ agonist, troglitazone; the PPARα agonist, Wy-14643, and bezafibrate were also able to inhibit TGF-β-induced CTGF. The results suggest that 15d-PGJ2 inhibits TGF-β-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.
頁(從 - 到)22-27
期刊Toxicology Letters
出版狀態已發佈 - 五月 22 2009

ASJC Scopus subject areas

  • Toxicology

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