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CC BY-NC-ND 4.0 · Semin Liver Dis 2024; 44(01): 099-114
DOI: 10.1055/a-2275-0408
DOI: 10.1055/a-2275-0408
Review Article
GAS6/TAM Axis as Therapeutic Target in Liver Diseases
Funding This research was funded by Instituto de Salud Carlos III (Project# PI22/00475 to M.M.) and by Ministerio de Ciencia e Innovación (PID2021-123564OB-I00, MCIN/AEI/10.13039/501100011033 to A.M. and P.G.F.), and co-funded by the European Union “ERDF A Way of Making Europe” (Next Generation EU/PRTR); CIBERCV; AGAUR (2021_SGR_490) and CERCA Programme/Generalitat de Catalunya; and Fundació la Marató de TV3 (202133-32) to A.M. and P.G.F. This research also received research funding and Sponsored Research Agreement, from BerGenBio ASA.
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.
Publication History
Accepted Manuscript online:
23 February 2024
Article published online:
21 March 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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