Department of Biomaterials Science and Technology, Faculty of Science and Technology, Technical Medical Centre, University of Twente, Enschede 7500, the Netherlands.
World J Gastroenterol. 2020 Mar 14;26(10):1005-1019. doi: 10.3748/wjg.v26.i10.1005.
Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase expressed in most hematopoietic cells and non-hematopoietic cells and play a crucial role in both immune and non-immune biological responses. SYK mediate diverse cellular responses an immune-receptor tyrosine-based activation motifs (ITAMs)-dependent signalling pathways, ITAMs-independent and ITAMs-semi-dependent signalling pathways. In liver, SYK expression has been observed in parenchymal (hepatocytes) and non-parenchymal cells (hepatic stellate cells and Kupffer cells), and found to be positively correlated with the disease severity. The implication of SYK pathway has been reported in different liver diseases including liver fibrosis, viral hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis and hepatocellular carcinoma. Antagonism of SYK pathway using kinase inhibitors have shown to attenuate the progression of liver diseases thereby suggesting SYK as a highly promising therapeutic target. This review summarizes the current understanding of SYK and its therapeutic implication in liver diseases.
脾酪氨酸激酶（SYK）是一种在大多数造血细胞和非造血细胞中表达的非受体酪氨酸激酶，在免疫和非免疫生物反应中都发挥着关键作用。SYK 通过免疫受体酪氨酸激活基序（ITAMs）依赖性信号通路、非 ITAMs 依赖性和 ITAMs 半依赖性信号通路介导多种细胞反应。在肝脏中，已经观察到 SYK 在实质细胞（肝细胞）和非实质细胞（肝星状细胞和库普弗细胞）中的表达，并发现其与疾病严重程度呈正相关。SYK 途径的意义已在包括肝纤维化、病毒性肝炎、酒精性肝病、非酒精性脂肪性肝炎和肝细胞癌在内的不同肝病中得到报道。使用激酶抑制剂拮抗 SYK 途径已被证明可以减轻肝病的进展，从而表明 SYK 是一个极具前景的治疗靶点。本综述总结了目前对 SYK 的认识及其在肝脏疾病中的治疗意义。
