A transcriptional regulatory network of HNF4α and HNF1α involved in human diseases and drug metabolism

HNF4 alpha and HNF1 alpha are core transcription factors involved in the development and progression of a variety of human diseases and drug metabolism. They play critical roles in maintaining the normal growth and function of multiple organs, mainly the liver, and in the metabolism of endogenous and exogenous substances. The twelve isoforms of HNF4 alpha may exhibit different physiological functions, and HNF4 alpha and HNF1 alpha show varying or even opposing effects in different types of diseases, particularly cancer. Additionally, the regulation of CYP450, phase II drug-metabolizing enzymes, and drug transporters is affected by several factors. This article aims to review the role of HNF4 alpha and HNF1 alpha in human diseases and drug metabolism, including their structures and physiological functions, affected diseases, regulated drug metabolism genes, influencing factors, and related mechanisms. We also propose a transcriptional regulatory network of HNF4 alpha and HNF1 alpha that regulates the expression of target genes related to disease and drug metabolism.