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Gas6/TAM Axis in Sepsis: Time to Consider Its Potential Role as a Therapeutic Target

机译:败血症中的Gas6 / Tam轴:是时候考虑其作为治疗目标的潜在作用的时间

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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.
机译:酪氨酸激酶受体是涉及细胞信号传导和相互作用的跨膜蛋白。其中,TAM系列(由Tyro 3,AXL和MER组成)代表了许多生理和病理条件中具有重要作用的特殊亚组。尽管不同的活化机制(例如,蛋白质S和半乳糖蛋白-3),但TAM作用与其共同的配体紧密相关,该蛋白质称为生长抑制的6(Gas6)。由于TAM和Gas6的表达在组织中被广泛分布,因此这些组分之一的任何改变都可以导致不同的病理条件。此外,由于它们是稳态维护不可或缺的,近年来,在调控炎症过程中的作用,近年来越来越多的兴趣。由于这种参与,许多作者已经证明了Gas6 / TAM轴在败血症和败血症相关炎症反应中的枢转作用。在这一叙述审查中,我们突出了目前的知识以及对不同临床病症的谭和Gas6的最后发现,特别是在败血症和脓毒症休克中。最后,不仅在某些全身急性条件下的诊断和预后生物标志物而强调了Gas6作为诊断和预后生物标志物,而且在这些危及生命的疾病中潜在的治疗作用。

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