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Int. J. Mol. Sci. 2014, 15(4), 5412-5425; doi:10.3390/ijms15045412

Signal Transduction of Platelet-Induced Liver Regeneration and Decrease of Liver Fibrosis

Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
Author to whom correspondence should be addressed.
Received: 23 February 2014 / Revised: 16 March 2014 / Accepted: 20 March 2014 / Published: 28 March 2014
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)
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Platelets contain three types of granules: alpha granules, dense granules, and lysosomal granules. Each granule contains various growth factors, cytokines, and other physiological substances. Platelets trigger many kinds of biological responses, such as hemostasis, wound healing, and tissue regeneration. This review presents experimental evidence of platelets in accelerating liver regeneration and improving liver fibrosis. The regenerative effect of liver by platelets consists of three mechanisms; i.e., the direct effect on hepatocytes, the cooperative effect with liver sinusoidal endothelial cells, and the collaborative effect with Kupffer cells. Many signal transduction pathways are involved in hepatocyte proliferation. One is activation of Akt and extracellular signal-regulated kinase (ERK)1/2, which are derived from direct stimulation from growth factors in platelets. The other is signal transducer and activator of transcription-3 (STAT3) activation by interleukin (IL)-6 derived from liver sinusoidal endothelial cells and Kupffer cells, which are stimulated by contact with platelets during liver regeneration. Platelets also improve liver fibrosis in rodent models by inactivating hepatic stellate cells to decrease collagen production. The level of intracellular cyclic adenosine monophosphate (cyclic AMP) is increased by adenosine through its receptors on hepatic stellate cells, resulting in inactivation of these cells. Adenosine is produced by the degradation of adenine nucleotides such as adenosine diphosphate (ADP) and adenosine tri-phosphate (ATP), which are stored in abundance within the dense granules of platelets.
Keywords: platelet; STAT3; Akt; ERK1/2; S1P; adenosine; cyclic AMP platelet; STAT3; Akt; ERK1/2; S1P; adenosine; cyclic AMP
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Murata, S.; Maruyama, T.; Nowatari, T.; Takahashi, K.; Ohkohchi, N. Signal Transduction of Platelet-Induced Liver Regeneration and Decrease of Liver Fibrosis. Int. J. Mol. Sci. 2014, 15, 5412-5425.

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