Department of Biochemistry, University of Oslo, Oslo, Norway.
Proteomics Clin Appl. 2014 Jun;8(5-6):438-46. doi: 10.1002/prca.201300078. Epub 2014 Mar 26.
Factor VII activating protease (FSAP) is a multifunctional serine protease that is mainly synthesized and secreted by hepatocytes. This enzyme is highly evolutionarily conserved and contains three epidermal growth factor like domains, a kringle domain and a trypsin-like serine protease signature at its C-terminus. Animal experimentation and clinical findings indicate that FSAP influences a range of inflammatory fibroproliferative diseases. In particular, recent work demonstrated that FSAP is anti-fibrotic and influences liver fibrosis progression. The relative high physiological concentration, occurrence of gene variants affecting the proteolytic activity of FSAP and eclectic substrate specificity should in principal presuppose this protease to be frequently found in studies in which quantitative proteomics is performed. However, presently there are only a few studies available that have identified FSAP in applications using 2D gels, MS or other proteomic-associated techniques. We summarize here the actual knowledge about FSAP functions in initiation and progression of hepatic fibrosis and comment on proteome studies in which altered expression or activity of FSAP was reported.
因子 VII 激活蛋白酶 (FSAP) 是一种多功能丝氨酸蛋白酶,主要由肝细胞合成和分泌。这种酶具有高度的进化保守性,包含三个表皮生长因子样结构域、一个kringle 结构域和一个位于 C 末端的胰蛋白酶样丝氨酸蛋白酶特征。动物实验和临床发现表明,FSAP 影响多种炎症性纤维增生性疾病。特别是,最近的研究表明,FSAP 具有抗纤维化作用,并影响肝纤维化的进展。相对较高的生理浓度、影响 FSAP 蛋白水解活性的基因变异的发生以及独特的底物特异性,应该假定这种蛋白酶在进行定量蛋白质组学研究的研究中经常被发现。然而,目前只有少数研究使用 2D 凝胶、MS 或其他与蛋白质组学相关的技术鉴定了 FSAP。我们在这里总结了 FSAP 在肝纤维化发生和进展中的作用的现有知识,并对报道 FSAP 表达或活性改变的蛋白质组学研究进行了评论。