Role of spleen tyrosine kinase in liver diseases

Abstract

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 via 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.