Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Lodoxamide Attenuates Hepatic Fibrosis in Mice: Involvement of GPR35

  • Kim, Mi-Jeong (College of Pharmacy, Pusan National University) ;
  • Park, Soo-Jin (College of Pharmacy, Pusan National University) ;
  • Nam, So-Yeon (College of Pharmacy, Pusan National University) ;
  • Im, Dong-Soon (College of Pharmacy, Pusan National University)
  • Received : 2018.11.26
  • Accepted : 2019.05.21
  • Published : 2019.12.30
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Abstract

A previous pharmacogenomic analysis identified cromolyn, an anti-allergic drug, as an effective anti-fibrotic agent that acts on hepatocytes and stellate cells. Furthermore, cromolyn was shown to be a G protein-coupled receptor 35 (GPR35) agonist. However, it has not been studied whether anti-fibrotic effects are mediated by GPR35. Therefore, in this study, the role of GPR35 in hepatic fibrosis was investigated through the use of lodoxamide, another anti-allergic drug and a potent GPR35 agonist. Long-term treatment with carbon tetrachloride induced hepatic fibrosis, which was inhibited by treatment with lodoxamide. Furthermore, CID2745687, a specific GPR35 antagonist, reversed lodoxamide-mediated anti-fibrotic effects. In addition, lodoxamide treatment showed significant effects on the mRNA expression of collagen Iα1, collagen Iα2, and TGF-β1 in the extracellular matrix. However, a transforming growth factor α (TGF-α) shedding assay revealed lodoxamide not to be a potent agonist of mouse GPR35 in vitro. Therefore, these results showed anti-fibrotic effects of lodoxamide in mice and raise concerns how lodoxamide protects against liver fibrosis in vivo and whether GPR35 is involved in the action.

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References

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