Kikuchi Wataru, Nishimura Motoi, Kuga Takahisa, Tsuchida Sachio, Saito Tatsuya, Satoh Mamoru, Noda Kenta, Kodera Yoshio, Tomonaga Takeshi, Nomura Fumio
Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan ; R&D Department, Nittobo Medical Co., Ltd., Koriyama, Japan.
Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
Clin Proteomics. 2016 Oct 7;13:27. doi: 10.1186/s12014-016-9129-6. eCollection 2016.
Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9) is a new serum biomarker for chronic hepatitis that was discovered by proteomics analysis. Previous studies have shown that FIC5.9 is derived from the C-terminal region of fibrinogen alpha chain and the serum levels of FIC5.9 decrease in chronic hepatitis. It also have been reported that FIC5.9 cannot be detected in the blood stream of the systemic circulation and it is released from fibrinogen during blood clotting in collecting tube. However, the mechanism of FIC5.9 releasing from fibrinogen is unclear.
We formulated a hypothesis that FIC5.9 is released by enzymes that are activated by post-blood collection and may be coagulation and fibrinolysis factors. In this study, we analyzed the mechanisms of FIC5.9 releasing from fibrinogen in healthy blood.
Our analysis showed that thrombin acts as an initiator for FIC5.9 releasing, and that mainly plasmin cleaves N-terminal end of FIC5.9 and neutrophil elastase cleave C-terminal end of FIC5.9.
FIC5.9 reflects minute changes in coagulation and fibrinolysis factors and may be associated with pathological conditions.
纤维蛋白原α C链5.9 kDa片段(FIC5.9)是通过蛋白质组学分析发现的一种用于慢性肝炎的新型血清生物标志物。先前的研究表明,FIC5.9源自纤维蛋白原α链的C末端区域,且慢性肝炎患者血清中FIC5.9水平降低。也有报道称,在体循环的血流中检测不到FIC5.9,它是在采血管中血液凝固过程中从纤维蛋白原释放出来的。然而,FIC5.9从纤维蛋白原释放的机制尚不清楚。
我们提出一个假设,即FIC5.9是由采血后被激活的酶释放的,这些酶可能是凝血因子和纤溶因子。在本研究中,我们分析了健康血液中FIC5.9从纤维蛋白原释放的机制。
我们的分析表明,凝血酶是FIC5.9释放的启动因子,主要是纤溶酶切割FIC5.9的N末端,中性粒细胞弹性蛋白酶切割FIC5.9的C末端。
FIC5.9反映了凝血因子和纤溶因子的微小变化,可能与病理状况有关。