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 (CCl4) 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 CCl4 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 CCl4 for 48h 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.

• Authors: Tsutomu Minamino, Yoshiya Ito, Hirotoki Ohkubo, Yuki Shimuzu, Ken Kojo, Nobuyuki Nishizwa, Hideki Amano, Shuh Narumiya, Wasaburo Koizumi, Masataka Majima
• Journal: Life sciences (Life Sci) Vol. 132 Pg. 85-92 (Jul 01 2015) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 25921763 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• DNA Primers
• Receptors, Thromboxane A2, Prostaglandin H2
• Hepatocyte Growth Factor
• Carbon Tetrachloride

Topics

• Analysis of Variance
• Animals
• Carbon Tetrachloride
• Chemical and Drug Induced Liver Injury (metabolism, physiopathology)
• DNA Primers (genetics)
• Hepatocyte Growth Factor (metabolism)
• Human Umbilical Vein Endothelial Cells
• Humans
• Immunohistochemistry
• Liver Regeneration (physiology)
• Male
• Mice
• Mice, Knockout
• Platelet Adhesiveness (physiology)
• Real-Time Polymerase Chain Reaction
• Receptors, Thromboxane A2, Prostaglandin H2 (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (physiology)