Adhesion of platelets through thromboxane A2 receptor signaling facilitates liver repair during acute chemical-induced hepatotoxicity

Abstract Aims Platelets have been suggested to play an important role in liver regeneration and repair after hepatic resection and acute liver injury. However, the underlying mechanisms of liver repair remain elusive. Signaling through thromboxane prostanoid (TP) receptor participates in inflammation and tissue injury through platelet aggregation. On the other hand, TP receptor signaling also is involved in tissue repair and tumor growth through angiogenesis. The present study was examined whether or not TP receptor signaling contributes to liver repair and sinusoidal restoration from acute liver injury through platelet adhesion to the hepatic sinusoids. Main methods Carbon tetrachrolide (CCl 4 ) was used to induce acute liver injury in TP receptor knockout mice (TP −/− mice) and their wild-type littermates (WT mice). Key findings Compared with WT mice, TP −/− mice exhibited delayed in liver repair and sinusoidal restoration after CCl 4 treatment, which were associated with attenuated hepatic expression of pro-angiogenic factors. Intravital microscopic observation revealed that adhering platelets to the sinusoids was increased in WT livers during the repair phase as compared with TP −/− livers, and platelet adhesion was dependent on TP receptor signaling. The levels of hepatocyte growth factor (HGF) in platelets from WT mice treated with CCl 4 for 48 h were greater than those form TP −/− mice, and HGF enhanced the expression of angiogenic factors in cultured human umbilical vein endothelial cells (HUVECs). Significance These results suggested that TP receptor signaling facilitates liver repair and sinusoidal restoration from acute liver injury through HGF release from platelets adhering to the sinusoids.