Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner.
Int J Mol Sci
; 24(6)2023 Mar 19.
Article
in En
| MEDLINE
| ID: mdl-36982915
ABSTRACT
Resmetirom, a liver-directed, orally active agonist of THR-ß, could play a favorable role in treating NASH, but little is known about the underlying mechanism. A NASH cell model was established to test the preventive effect of resmetirom on this disease in vitro. RNA-seq was used for screening, and rescue experiments were performed to validate the target gene of the drug. A NASH mouse model was used to further elucidate the role and the underlying mechanism of resmetirom. Resmetirom effectively eliminated lipid accumulation and decreased triglyceride (TG) levels. In addition, repressed RGS5 in the NASH model could be recovered by resmetirom treatment. The silencing of RGS5 effectively impaired the role of resmetirom. In the NASH mouse model, obvious gray hepatization, liver fibrosis and inflammation, and increased macrophage infiltration were observed in liver tissues, while resmetirom almost returned them to normal conditions as observed in the control group. Pathological experimental data also confirmed that resmetirom has great potential in NASH treatment. Finally, RGS5 expression was suppressed in the NASH mouse model, but it was upregulated by resmetirom treatment, while the STAT3 and NF-κB signaling pathways were activated in NASH but inhibited by the agent. Resmetirom could improve NASH by recovering RGS5 expression and subsequently inactivating the STAT3 and NF-κB signaling pathways.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RGS Proteins
/
Non-alcoholic Fatty Liver Disease
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Int J Mol Sci
Year:
2023
Type:
Article
Affiliation country:
China