title: Novel functions of platelets in the liver.
abstract: Platelets contain not only proteins needed for hemostasis but also many growth factors that are required for organ development, tissue regeneration, and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease (CLD) and cirrhosis, is due to various causes, such as decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis and the role of platelets in CLD are poorly understood. Thus, in this paper, the experimental evidence for platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. Platelets improve liver fibrosis by inactivating hepatic stellate cells to decrease collagen production. The level of intracellular cAMP is increased by adenosine through its receptors on hepatic stellate cells, thereby resulting in inactivation of these cells. Adenosine is produced by degradation of adenine nucleotides, which are stored in abundance within the dense granules of platelets. The regenerative effect of platelets in the liver consists of three mechanisms: a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these experiments, a clinical trial suggested that the increase in platelets induced by platelet transfusion improved liver function in patients with CLD in a clinical setting.We highlight the current knowledge concerning the role of platelets in CLD and expect to open a novel avenue for application of these clinical therapies to treat liver disease.
authors.affiliation: Department of Surgery, Division of Gastroenterological and Hepatobiliary Surgery, and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Tomohiro
authors.identifier: http://orcid.org/0000-0002-7932-8724
authors.initials: T
authors.lastname: Kurokawa
authors.affiliation: Department of Surgery, Division of Gastroenterological and Hepatobiliary Surgery, and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yun-Wen
authors.initials: YW
authors.lastname: Zheng
authors.affiliation: Department of Surgery, Division of Gastroenterological and Hepatobiliary Surgery, and Organ Transplantation, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ohkohchi
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000378:metabolism; D006801:Humans; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*; D008115:Liver Regeneration; D017713:Platelet Transfusion; D013921:Thrombocytopenia / Q000209:etiology; D013926:Thrombopoietin / Q000378:metabolism
chemical_list: D000227:Adenine Nucleotides; D003094:Collagen; D013926:Thrombopoietin; D000242:Cyclic AMP
keywords: Kupffer cell; adenosine tri-phosphate (ATP); blood transfusion; chronic liver disease; cirrhosis; eltrombopag; hepatocyte growth factor (HGF); liver; liver regeneration; liver sinusoidal endothelial cell (LSEC); platelet; thrombocytopenia; thrombopoietin