Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P15088 (
mast cell
)
14,925
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Although
GPR35
is an orphan G protein-coupled receptor, synthetic agonists and antagonists have been developed. Recently, cromolyn, a
mast cell
stabilizer, was reported as an agonist of
GPR35
and was shown to exhibit antifibrotic effects through its actions on hepatocytes and stellate cells. In this study, the role of
GPR35
in hepatic steatosis was investigated using an in vitro model of liver X receptor (LXR)-mediated hepatocellular steatosis and an in vivo model of high fat diet-induced liver steatosis.
GPR35
was expressed in Hep3B human hepatoma cells and mouse primary hepatocytes. A specific LXR activator, T0901317, induced lipid accumulation in Hep3B cells. Lodoxamide, the most potent agonist of
GPR35
, inhibited lipid accumulation in a concentration-dependent manner. The protective effect of lodoxamide was inhibited by a specific
GPR35
antagonist, CID2745687, and by siRNA-mediated knockdown of
GPR35
. The expression of SREBP-1c, a key transcription factor for lipid synthesis, was induced by T0901317 and the induction was inhibited by lodoxamide. Through the use of specific inhibitors of cellular signaling components, the lodoxamide-induced inhibition of lipid accumulation was found to be mediated through p38 MAPKs and JNK, but not through G
i/o
proteins and ERKs. Furthermore, the protective effect of lodoxamide was confirmed in mouse primary hepatocytes. Lodoxamide suppressed high fat diet-induced fatty liver development, which suggested the protective function of
GPR35
in liver steatosis. Therefore, the present data suggest that
GPR35
may function to protect against fatty liver development.
...
PMID:Protective effect of lodoxamide on hepatic steatosis through GPR35. 3030 98
