Role of spleen tyrosine kinase in liver diseases

Table 2 Spleen tyrosine kinase inhibitors implicated in liver diseases

Inhibitor	Mechanism of action	Therapeutic effect	Ref.
R406	Blocking of Fc receptor signalling pathway, NF-κB signalling pathway and inflammasome activation	Reduced SYK expression and phosphorylation resulting in attenuated liver steatosis, inflammation and fibrosis in ASH and NASH murine models	[20,44]
GS-9973	Decreased expression of HSCs activation (CBP, MYB, MYC) and HSCs proliferation factors (MYC and CCND1)	Inhibition of HSCs proliferation and HSC activation resulting in amelioration of fibrosis and hepatocarcinogenesis	[28]
PRT062607 and piceatannol	Increased intra-tumoral p16, p53 and decreased expression of Bcl-xL and SMAD4. Decreased expression of genes regulating angiogenesis, apoptosis, cell cycle regulation and cellular senescence. Down-regulation of mTOR, IL-8 signalling and oxidative phosphorylation	Reduced HSCs differentiation and infiltration of inflammatory cells including T cells, B cells and myeloid cells, reduced oncogenic progression. Marked attenuation of toxin-induced liver fibrosis, associated hepatocellular injury, intra-hepatic inflammation and hepatocarcinogenesis	[128]

SYK: Spleen tyrosine kinase; NASH: Non-alcoholic steatohepatitis; ASH: Alcoholic steatohepatitis; HSCs: Hepatic stellate cells; IL-8: Interleukin-8.