Lodoxamide Attenuates Hepatic Fibrosis in Mice: Involvement of GPR35
10.4062/biomolther.2018.227
- Author:
Mi-Jeong KIM
1
;
Soo-Jin PARK
;
So-Yeon NAM
;
Dong-Soon IM
Author Information
1. College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2020;28(1):92-97
- CountryRepublic of Korea
- Language:0
-
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 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.
