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Published on: June 14, 2024
Gas6/TAM Axis in Sepsis: Time to Consider Its Potential Role as a Therapeutic Target
Livia Salmi1, Francesco Gavelli1, Filippo Patrucco1
1Department of Translational Medicine, University of Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy.
Abstract:
Tyrosine kinase receptors are transmembrane proteins involved in cell signaling and interaction. Among them, the TAM family (composed by Tyro 3, Axl, and Mer) represents a peculiar subgroup with an important role in many physiological and pathological conditions. Despite different mechanisms of activation (e.g., protein S and Galactin-3), TAM action is tightly related to their common ligand, a protein named growth arrest-specific 6 (Gas6). Since the expression of both TAM and Gas6 is widely distributed among tissues, any alteration of one of these components can lead to different pathological conditions. Moreover, as they are indispensable for homeostasis maintenance, in recent years a growing interest has emerged regarding their role in the regulation of the inflammatory process. Due to this involvement, many authors have demonstrated the pivotal role of the Gas6/TAM axis in both sepsis and the sepsis-related inflammatory responses. In this narrative review, we highlight the current knowledge as well as the last discoveries on TAM and Gas6 implication in different clinical conditions, notably in sepsis and septic shock. Lastly, we underline not only the feasible use of Gas6 as a diagnostic and prognostic biomarker in certain systemic acute conditions but also its potential therapeutic role in these life-threatening diseases.
Insights
The Gas6/TAM signaling pathway is crucial for maintaining homeostasis and regulating inflammation. This review explores its role in sepsis and septic shock, highlighting Gas6 as a potential biomarker and therapeutic target.
Area of Science:
- Cellular Biology
- Molecular Medicine
- Immunology
Background:
- Tyrosine kinase receptors, including the TAM family (Tyro 3, Axl, Mer), are key in cell signaling.
- The TAM family shares a common ligand, growth arrest-specific 6 (Gas6), influencing physiological and pathological processes.
- Dysregulation of the Gas6/TAM axis is implicated in various diseases due to their widespread tissue distribution.
Purpose of the Study:
- To review current knowledge on the role of TAM receptors and Gas6 in clinical conditions.
- To highlight recent discoveries concerning the Gas6/TAM axis in sepsis and septic shock.
- To explore the potential of Gas6 as a diagnostic, prognostic, and therapeutic agent.
Main Methods:
- Narrative review of existing literature.
- Analysis of studies focusing on the Gas6/TAM axis in inflammation and sepsis.
- Synthesis of findings on biomarker and therapeutic potential.
Main Results:
- The Gas6/TAM axis plays a pivotal role in sepsis-related inflammatory responses.
- Alterations in Gas6 or TAM expression can lead to pathological conditions.
- Gas6 is involved in maintaining homeostasis and regulating inflammation.
Conclusions:
- The Gas6/TAM axis is significantly implicated in sepsis pathogenesis and progression.
- Gas6 shows promise as a diagnostic and prognostic biomarker for systemic acute conditions.
- Targeting the Gas6/TAM pathway may offer therapeutic strategies for sepsis and septic shock.
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