从人类基因组发现新细胞因子的研究进展

Progress in the discovery of novel cytokines from human genome

细胞因子是具有重要生理病理功能的小分子分泌蛋白,在新药开发领域,细胞因子药物取得了巨大的成功,2017年全球前十位最畅销药物中有5个是细胞因子或其受体抑制剂。细胞因子研究中最具原创性和挑战性的工作是发现新的具有重要功能和药物开发前景的新细胞因子。在后基因组时代,利用反向生物学技术,国际上已经发现了一批新细胞因子,数个新细胞因子药物被批准上市。本综述重点介绍笔者实验室从人类基因组发现的10个新细胞因子,包括CTRP4、CCDC134、PSMP、VSTM1-v2、FAM3D、TMEM98、CSBF/C10orf99、FAM19A4、FAM19A5、FAM19A1。其中一些新细胞因子已经显示具有重要的生理病理功能,鉴定了功能性受体,或开展了临床标本分析及动物体内实验,为进一步临床应用研究奠定了基础。

Cytokines are small secreted proteins that play an important role in physiological and pathological processes. In the field of pharmacological development, cytokine drugs have achieved great success. In 2017 , five of the world's top ten best-selling drugs were inhibitors of cytokines or their receptors. The most innovative and challenging work in cytokine research is the discovery of novel cytokines with important functions and potential druggable prospects. In the post-genome era, a number of novel cytokines have been internationally discovered using reverse biology techniques, and from which, several cytokine drugs have been approved for marketing. This review highlights 10 novel cytokines found in the human genome by the author's laboraton , including CTRP4, CCDC134, PSMP, VSTMl-v2, FAM3D, TMEM98, CSBF/ C10orf99, FAM19A4, FAM 19A5 and FAM19A1. Some of them have been shown to have important physiological and pathological functions. Identification of functional receptors, clinical specimen analysis or in vivo animal experiment has been carried out for them, which lays the foundation for further research in their clinical applications.