Schanbacher Constanze, Hermanns Heike M, Lorenz Kristina, Wajant Harald, Lang Isabell
Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany.
Department of Internal Medicine II, Division of Hepatology, University Hospital Würzburg, Auvera Haus, Grombühlstrasse 12, 97080 Würzburg, Germany.
Biomedicines. 2023 Feb 14;11(2):559. doi: 10.3390/biomedicines11020559.
Adiponectin and the other 15 members of the complement 1q (C1q)/tumor necrosis factor (TNF)-related protein (CTRP) family are secreted proteins composed of an N-terminal variable domain followed by a stalk region and a characteristic C-terminal trimerizing globular C1q (gC1q) domain originally identified in the subunits of the complement protein C1q. We performed a basic PubMed literature search for articles mentioning the various CTRPs or their receptors in the abstract or title. In this narrative review, we briefly summarize the biology of CTRPs and focus then on the structure, receptors and major signaling pathways of CTRPs. Analyses of CTRP knockout mice and CTRP transgenic mice gave overwhelming evidence for the relevance of the anti-inflammatory and insulin-sensitizing effects of CTRPs in autoimmune diseases, obesity, atherosclerosis and cardiac dysfunction. CTRPs form homo- and heterotypic trimers and oligomers which can have different activities. The receptors of some CTRPs are unknown and some receptors are redundantly targeted by several CTRPs. The way in which CTRPs activate their receptors to trigger downstream signaling pathways is largely unknown. CTRPs and their receptors are considered as promising therapeutic targets but their translational usage is still hampered by the limited knowledge of CTRP redundancy and CTRP signal transduction.
脂联素以及补体1q（C1q）/肿瘤坏死因子（TNF）相关蛋白（CTRP）家族的其他15个成员都是分泌蛋白，由一个N端可变结构域、一个柄状区域和一个特征性的C端三聚化球状C1q（gC1q）结构域组成，该结构域最初在补体蛋白C1q的亚基中被鉴定出来。我们在PubMed上进行了基本的文献检索，查找摘要或标题中提及各种CTRP或其受体的文章。在这篇叙述性综述中，我们简要总结了CTRP的生物学特性，然后重点关注CTRP的结构、受体和主要信号通路。对CTRP基因敲除小鼠和CTRP转基因小鼠的分析提供了压倒性的证据，证明CTRP在自身免疫性疾病、肥胖、动脉粥样硬化和心脏功能障碍中的抗炎和胰岛素增敏作用具有相关性。CTRP形成同型和异型三聚体及寡聚体，它们可能具有不同的活性。一些CTRP的受体尚不清楚，一些受体被几种CTRP冗余靶向。CTRP激活其受体以触发下游信号通路的方式在很大程度上尚不清楚。CTRP及其受体被认为是有前景的治疗靶点，但由于对CTRP冗余和CTRP信号转导的了解有限，它们在临床转化中的应用仍然受到阻碍。
