title: Platelet-derived adenosine 5'-triphosphate suppresses activation of human hepatic stellate cell: In vitro study.
abstract: OBJECTIVE
  Activated hepatic stellate cells (HSC) play a critical role in liver fibrosis. Suppressing abnormal function of HSC or reversion from activated to quiescent form is a hopeful treatment for liver cirrhosis. The interaction between platelets and HSC remains unknown although platelets go through hepatic sinusoids surrounded by HSC. This study aimed at clarifying the hypothesis that platelets control activation of HSC.
  
  
  METHODS
  We used human platelets, platelet extracts, and primary or immortalized human HSC. We examined the effect of platelets on the activation, DNA synthesis, type I collagen production, and fibrosis-relating gene expressions of HSC. We investigated what suppressed activation of HSC within platelets and examined the mechanism of controlling activation in vitro.
  
  
  RESULTS
  Platelets and platelet extracts suppressed activation of HSC. Platelets decreased type I collagen production without affecting DNA synthesis. Platelets increased the expression of matrix metallopeptidase 1. As platelet extracts co-cultured with an enzyme of degrading adenosine 5'-triphosphate (ATP) suppressed activation, we detected adenine nucleotides within platelets or on their surfaces and confirmed the degradation of adenine nucleotides by HSC and the production of adenosine. Adenosine and platelets increased the intracellular cyclic adenosine 5'-monophosphate (cAMP), which is important in quiescent HSC. A great amount of adenosine and ATP also suppressed activation of HSC.
  
  
  CONCLUSIONS
  Activation of human HSC is suppressed by human platelets or platelet-derived ATP via adenosine-cAMP signaling pathway in vitro. Therefore, platelets have the possibility to be used in the treatment of liver cirrhosis.
authors: Departments of Surgery             Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors: Naoya
authors: N
authors: Ikeda
authors: Soichiro
authors: S
authors: Murata
authors: Takehito
authors: T
authors: Maruyama
authors: Takafumi
authors: T
authors: Tamura
authors: Reiji
authors: R
authors: Nozaki
authors: Takuya
authors: T
authors: Kawasaki
authors: Kiyoshi
authors: K
authors: Fukunaga
authors: Tatsuya
authors: T
authors: Oda
authors: Ryoko
authors: R
authors: Sasaki
authors: Masato
authors: M
authors: Homma
authors: Nobuhiro
authors: N
authors: Ohkohchi