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Lodoxamide Attenuates Hepatic Fibrosis in Mice: Involvement of GPR35

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. Longterm 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 I?1, collagen I?2, and TGF-?1 in the extracellular matrix. However, a transforming growth factor ? (TGF-?) 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.

SUBMITTER: Kim MJ

PROVIDER: S-EPMC6939691 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Lodoxamide Attenuates Hepatic Fibrosis in Mice: Involvement of GPR35

Kim Mi-Jeong MJ Park Soo-Jin SJ Nam So-Yeon SY Im Dong-Soon DS

Biomolecules & therapeutics 20200101 1

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. ...[more]

PMID: 31189299

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Lodoxamide Attenuates Hepatic Fibrosis in Mice: Involvement of GPR35

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Lodoxamide Attenuates Hepatic Fibrosis in Mice: Involvement of GPR35

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