Insights of Direct and Indirect Regulation of PXR through Phosphorylation in Fatty Liver Disease

Autor: Basaly, Veronia, Bhattacharya, Anisha, Guo, Grace L.
Zdroj: Molecular Pharmacology; 20240101, Issue: Preprints
Abstrakt: The Pregnane X receptor, a ligand-activated nuclear receptor, regulates the transcription of several genes that encode many enzymes and transporters related to drug metabolism. PXR also performs an important role as a physiological sensor in the modulation of endobiotic metabolism for hormones, bile acids, cholesterol, fatty acids, and glucose. Dysregulation of these PXR-mediated pathways is implicated in the progression of metabolic dysfunction associated steatohepatitis (MASH), contributing to the complex interplay of factors involved in chronic liver disease development and exacerbation affecting millions worldwide. This review highlights the current knowledge of PXR expression and its role in endobiotic metabolism related to MASH development, that is associated with diverse causes and dire outcomes. This review focuses on elucidating the molecular pathways associated with PXR activation directly or indirectly and PXR interaction with other regulatory factors. While there is still much to comprehend about the intricate details of these pathways, the conclusion is drawn that PXR exerts a crucial role in the pathological and physiological pathways of hepatic cellular processes, which holds promise as a potential pharmacological target for exploring novel therapeutic approaches for MASH treatment and/or prevention.
Databáze: Supplemental Index