Abstract
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.
Keywords
phagocytosis - fibrosis - inflammation - cytokine regulation - biomarkers