Abstract

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.

Original languageEnglish
Pages (from-to)22-27
Number of pages6
JournalToxicology Letters
Volume187
Issue number1
DOIs
Publication statusPublished - May 22 2009

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Transforming Growth Factors
Peroxisome Proliferator-Activated Receptors
Connective Tissue Growth Factor
Hepatocellular Carcinoma
Phosphorylation
troglitazone
Liver Cirrhosis
Liver
Bezafibrate
Ligands
JNK Mitogen-Activated Protein Kinases
Metabolites
15-deoxy-delta(12,14)-prostaglandin J2
Arachidonic Acid
Anti-Inflammatory Agents
Cells
Cytokines
Cell Line
Messenger RNA
Proteins

Keywords

  • 15-Deoxy-Δ-prostaglandin J
  • CTGF
  • Fibrosis
  • Hepatoma
  • TGF-β

ASJC Scopus subject areas

  • Toxicology

Cite this

15-Deoxy-Δ12,14-prostaglandin J2 inhibits fibrogenic response in human hepatoma cells. / Suk, Fat Moon; Chen, Chien Ho; Lin, Shyr Yi; Cheng, Ching Ju; Yen, Shish Jung; Hung, Ling Fang; Liu, Der Zen; Liang, Yu Chih.

In: Toxicology Letters, Vol. 187, No. 1, 22.05.2009, p. 22-27.

Research output: Contribution to journalArticle

Suk, Fat Moon ; Chen, Chien Ho ; Lin, Shyr Yi ; Cheng, Ching Ju ; Yen, Shish Jung ; Hung, Ling Fang ; Liu, Der Zen ; Liang, Yu Chih. / 15-Deoxy-Δ12,14-prostaglandin J2 inhibits fibrogenic response in human hepatoma cells. In: Toxicology Letters. 2009 ; Vol. 187, No. 1. pp. 22-27.
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abstract = "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.",
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T1 - 15-Deoxy-Δ12,14-prostaglandin J2 inhibits fibrogenic response in human hepatoma cells

AU - Suk, Fat Moon

AU - Chen, Chien Ho

AU - Lin, Shyr Yi

AU - Cheng, Ching Ju

AU - Yen, Shish Jung

AU - Hung, Ling Fang

AU - Liu, Der Zen

AU - Liang, Yu Chih

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N2 - 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.

AB - 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.

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