TAM (TYRO3, AXL, and MERTK) protein tyrosine kinase membrane receptors and their vitamin K-dependent ligands GAS6 and protein S (PROS) are well-known players in tumor biology and autoimmune diseases. In contrast, TAM regulation of fibrogenesis and the inflammation mechanisms underlying metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and, ultimately, liver cancer has recently been revealed. GAS6 and PROS binding to phosphatidylserine exposed in outer membranes of apoptotic cells links TAMs, particularly MERTK, with hepatocellular damage. In addition, AXL and MERTK regulate the development of liver fibrosis and inflammation in chronic liver diseases. Acute hepatic injury is also mediated by the TAM system, as recent data regarding acetaminophen toxicity and acute-on-chronic liver failure have uncovered. Soluble TAM-related proteins, mainly released from activated macrophages and hepatic stellate cells after hepatic deterioration, are proposed as early serum markers for disease progression. In conclusion, the TAM system is becoming an interesting pharmacological target in liver pathology and a focus of future biomedical research in this field.
Keyphrases
- liver failure
- tyrosine kinase
- oxidative stress
- induced apoptosis
- liver fibrosis
- hepatitis b virus
- cell cycle arrest
- drug induced
- epidermal growth factor receptor
- cell death
- room temperature
- liver injury
- magnetic resonance
- endoplasmic reticulum stress
- aortic dissection
- big data
- amino acid
- electronic health record
- cell proliferation
- single cell
- computed tomography
- artificial intelligence
- pi k akt
- small molecule