Platelet-derived adenosine 5′-triphosphate suppresses activation of human hepatic stellate cell: In vitro study

• Published in: Hepatology research 2012-01, Vol.42 (1), p.91-102
• Main Authors: Ikeda, Naoya, Murata, Soichiro, Maruyama, Takehito, Tamura, Takafumi, Nozaki, Reiji, Kawasaki, Takuya, Fukunaga, Kiyoshi, Oda, Tatsuya, Sasaki, Ryoko, Homma, Masato, Ohkohchi, Nobuhiro
• Format: Article
• Language: English
• Subjects: adenosine; adenosine 5′-triphosphate; cyclic adenosine 5′-monophosphate; hepatic stellate cell; liver fibrosis
• ISSN: 1386-6346; 1872-034X
• DOI: 10.1111/j.1872-034X.2011.00893.x

Aim:  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. Conclusion:  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.