Abstract
Nuclear receptors (NR) are ligand-modulated transcription factors that play diverse roles in cell differentiation, development, proliferation, and metabolism and are associated with numerous liver pathologies such as cancer, steatosis, inflammation, fibrosis, cholestasis, and xenobiotic/drug-induced liver injury. The network of target proteins associated with NRs is extremely complex, comprising coregulators, small noncoding microRNAs, and long noncoding RNAs. The importance of NRs as targets of liver disease is exemplified by the number of NR ligands that are currently used in the clinics or in clinical trials with promising results. Understanding the regulation by NR during pathophysiological conditions, and identifying ligands for orphan NR, points to a potential therapeutic approach for patients with liver diseases. An overview of complex NR metabolic networks and their pharmacological implications in liver disease is presented here.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 605-626 |
| Number of pages | 22 |
| Journal | Annual Review of Pharmacology and Toxicology |
| Volume | 56 |
| DOIs | |
| State | Published - Jan 6 2016 |
Funding
L.W. is supported by NIH R01DK080440, R01DK104656, R01ES025909, VA Merit Award 1I01BX002634, R21AA022482, and R21CA191507.
Keywords
- Cholestatic liver disease
- Drug-induced liver injury
- Hepatocellular cancer
- Liver inflammation and fibrosis
- Nonalcoholic fatty liver
- Viral hepatitis infection
ASJC Scopus subject areas
- Toxicology
- Pharmacology
