Apostolo Daria, D'Onghia Davide, Nerviani Alessandra, Ghirardi Giulia Maria, Sola Daniele, Perazzi Mattia, Tonello Stelvio, Colangelo Donato, Sainaghi Pier Paolo, Bellan Mattia
Department of Translational Medicine, University of Piemonte Orientale (UPO), 28100 Novara, Italy.
Centre for Experimental Medicine and Rheumatology, Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London E1 4NS, UK.
Curr Issues Mol Biol. 2024 Jul 15;46(7):7486-7504. doi: 10.3390/cimb46070444.
Systemic sclerosis (SSc) is a connective tissue disorder characterized by microvascular injury, extracellular matrix deposition, autoimmunity, inflammation, and fibrosis. The clinical complexity and high heterogeneity of the disease make the discovery of potential therapeutic targets difficult. However, the recent progress in the comprehension of its pathogenesis is encouraging. Growth Arrest-Specific 6 (Gas6) and Tyro3, Axl, and MerTK (TAM) receptors are involved in multiple biological processes, including modulation of the immune response, phagocytosis, apoptosis, fibrosis, inflammation, cancer development, and autoimmune disorders. In the present manuscript, we review the current evidence regarding SSc pathogenesis and the role of the Gas6/TAM system in several human diseases, suggesting its likely contribution in SSc and highlighting areas where further research is necessary to fully comprehend the role of TAM receptors in this condition. Indeed, understanding the involvement of TAM receptors in SSc, which is currently unknown, could provide valuable insights for novel potential therapeutic targets.
系统性硬化症（SSc）是一种结缔组织疾病，其特征为微血管损伤、细胞外基质沉积、自身免疫、炎症和纤维化。该疾病的临床复杂性和高度异质性使得发现潜在治疗靶点变得困难。然而，最近在理解其发病机制方面取得的进展令人鼓舞。生长停滞特异性蛋白6（Gas6）以及酪氨酸激酶受体3（Tyro3）、AXL受体酪氨酸激酶（Axl）和Mer酪氨酸激酶（MerTK，合称TAM）受体参与多种生物学过程，包括免疫反应调节、吞噬作用、细胞凋亡、纤维化、炎症、癌症发展和自身免疫性疾病。在本手稿中，我们综述了关于SSc发病机制的当前证据以及Gas6/TAM系统在几种人类疾病中的作用，表明其在SSc中的可能作用，并强调了为全面理解TAM受体在这种疾病中的作用而需要进一步研究的领域。事实上，了解目前尚不清楚的TAM受体在SSc中的作用，可能为新的潜在治疗靶点提供有价值的见解。
