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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靶标的潜在作用了

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摘要

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:酪氨酸激酶受体是参与细胞信号传导和相互作用的跨膜蛋白。其中,TAM家族(由Tyro 3,Axl和Mer组成)代表一个特殊的亚组,在许多生理和病理状况中起着重要作用。尽管有不同的激活机制(例如蛋白S和半乳糖3),但TAM的作用与它们的共同配体紧密相关,后者是一种称为生长停滞特异性6(Gas6)的蛋白质。由于TAM和Gas6的表达在组织之间广泛分布,因此这些成分之一的任何改变都可能导致不同的病理状况。此外,由于它们对于维持体内平衡是必不可少的,因此近年来,对于它们在调节炎症过程中的作用越来越引起关注。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的炎症反应中都起着关键作用。在本篇叙述性综述中,我们重点介绍了在不同临床情况下,尤其是败血症和败血性休克中TAM和Gas6含义的最新知识以及最新发现。最后,我们不仅强调在某些系统性急性疾病中将Gas6用作诊断和预后生物标志物的可行性,还强调了它在这些威胁生命的疾病中的潜在治疗作用。

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