Hepatocyte GPCR signaling regulates IRF3 to control hepatic stellate cell transdifferentiation.

ABSTRACT:

Background

Interferon Regulatory Factor 3 (IRF3) is a transcription factor that plays a crucial role in the innate immune response by recognizing and responding to foreign antigens. Recently, its roles in sterile conditions are being studied, as in metabolic and fibrotic diseases. However, the search on the upstream regulator for efficient pharmacological targeting is yet to be fully explored. Here, we show that G protein-coupled receptors (GPCRs) can regulate IRF3 phosphorylation through of GPCR-Gα protein interaction.

Results

IRF3 and target genes were strongly associated with fibrosis markers in liver fibrosis patients and models. Conditioned media from MIHA hepatocytes overexpressing IRF3 induced fibrogenic activation of LX-2 hepatic stellate cells (HSCs). In an overexpr

SUBMITTER: Yu JH 

PROVIDER: S-EPMC10795343 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature