title: Signal transduction of platelet-induced liver regeneration and decrease of liver fibrosis.
abstract: 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.
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. soichiro@md.tsukuba.ac.jp.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Murata
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. s1030518@u.tsukuba.ac.jp.
authors.forename: Takehito
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. s1130448@u.tsukuba.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nowatari
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. kazu1123@hh.iij4u.or.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. nokochi3@md.tsukuba.ac.jp.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ohkohchi
mesh_terms: D000241:Adenosine / Q000096:biosynthesis; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D042783:Endothelial Cells / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D055166:Hepatic Stellate Cells / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008103:Liver Cirrhosis / Q000473:pathology*; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000096:biosynthesis; D015398:Signal Transduction; D013926:Thrombopoietin / Q000378:metabolism
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013926:Thrombopoietin; D000242:Cyclic AMP; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D000241:Adenosine