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

Abstract

HNF4α and HNF1α 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 HNF4α may exhibit different physiological functions, and HNF4α and HNF1α 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 HNF4α and HNF1α 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 HNF4α and HNF1α that regulates the expression of target genes related to disease and drug metabolism.

Graphical Abstract

Keywords:

• HNF4α
• HNF1α
• human diseases
• drug metabolism
• CYP450

Acknowledgements

Figures 1–5 were created with BioRender.com with permission.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China under Grant No. 81760673; Qinghai Innovation Platform Construction Project under Grant No. 2021-ZJ-T03.