Northern Ireland Centre for Stratified Medicine, School of Biomedical Sciences, Ulster University, Altnagelvin Hospital Campus, C-TRIC Building Glenshane Road, Derry/Londonderry, Northern Ireland, UK.
Rev Endocr Metab Disord. 2022 Jun;23(3):449-462. doi: 10.1007/s11154-021-09688-4. Epub 2021 Sep 20.
TWEAK (tumor necrosis factor-like weak inducer of apoptosis) is a member of the TNF superfamily that controls a multitude of cellular events including proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation. TWEAK control of these events is via an expanding list of intracellular signalling pathways which include NF-κB, ERK/MAPK, Notch, EGFR and AP-1. Two receptors have been identified for TWEAK - Fn14, which targets the membrane bound form of TWEAK, and CD163, which scavenges the soluble form of TWEAK. TWEAK appears to elicit specific events based on the receptor to which it binds, tissue type in which it is expressed, specific extrinsic conditions, and the presence of other cytokines. TWEAK signalling is protective in healthy tissues, but in chronic inflammatory states become detrimental to the tissue. Consistent data show a role for the TWEAK/FN14/CD163 axis in metabolic disease, chronic autoimmune diseases, and acute ischaemic stroke. Low circulating concentrations of soluble TWEAK are predictive of poor cardiovascular outcomes in those with and without diabetes. This review details the current understanding of the TWEAK/Fn14/CD163 axis as one of the chief regulators of immune signalling and its cell-specific role in metabolic disease development and progression.
TWEAK（肿瘤坏死因子样凋亡弱诱导剂）是 TNF 超家族的一员，可控制多种细胞事件，包括增殖、迁移、分化、凋亡、血管生成和炎症。TWEAK 通过一系列不断扩展的细胞内信号通路来控制这些事件，包括 NF-κB、ERK/MAPK、Notch、EGFR 和 AP-1。已经鉴定出两种 TWEAK 的受体 - Fn14，其靶向 TWEAK 的膜结合形式，以及 CD163，其可清除 TWEAK 的可溶性形式。TWEAK 似乎根据其结合的受体、表达的组织类型、特定的外在条件以及其他细胞因子的存在，引发特定的事件。TWEAK 信号在健康组织中具有保护作用，但在慢性炎症状态下对组织有害。一致的数据表明，TWEAK/FN14/CD163 轴在代谢疾病、慢性自身免疫性疾病和急性缺血性中风中起作用。可溶性 TWEAK 的循环浓度低可预测有和没有糖尿病的患者心血管结局不良。这篇综述详细介绍了 TWEAK/Fn14/CD163 轴作为免疫信号的主要调节剂之一及其在代谢性疾病发展和进展中的细胞特异性作用的最新认识。
