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.
Highlights
CirrhosisCirrhosis is a serious and life-threatening major health problem worldwide
Platelets are translocated from the liver sinusoids to the space of Disse, and growth factors such as hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF) could be released through direct contact between platelets and hepatocytes (Figure 1)
These findings indicate that platelets suppress liver fibrosis by inactivating hepatic stellate cell (HSC)
Summary
Cirrhosis is a serious and life-threatening major health problem worldwide. It is an advanced form of hepatic fibrosis in response to chronic liver injury [1]. Liver transplantation is associated with donor shortage, surgical complications, organ rejection, and high cost [7,8,9,10,11]. Patients are often required to wait for many years for liver transplantation because of the shortage of donor organs, and some of them die while waiting. Treatment of cirrhosis consists of anti-inflammation, liver regeneration, and improvement of fibrosis. Each of these present very challenging problems in the clinical settings and no clear solutions have been found yet
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