Department of Pathology and Laboratory Medicine and UNC Blood Research Center, The University of North Carolina at Chapel Hill, NC, USA.
Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
Thromb Res. 2024 Oct;242:109134. doi: 10.1016/j.thromres.2024.109134. Epub 2024 Aug 28.
The plasma protein fibrinogen is encoded by 3 structural genes (FGA, FGB, and FGG) that are transcribed to mRNA, spliced, and translated to 3 polypeptide chains (Aα, Bβ, and γ, respectively). These chains are targeted for secretion, decorated with post-translational modifications, and assembled into a hexameric "dimer of trimers" (AαBβγ). Fully assembled fibrinogen is secreted into the blood as a 340 kDa glycoprotein. Fibrinogen is one of the most prevalent coagulation proteins in blood, and its expression is induced by inflammatory cytokines, wherein circulating fibrinogen levels may increase up to 3-fold during acute inflammatory events. Abnormal levels of circulating fibrinogen are associated with bleeding and thrombotic disorders, as well as several inflammatory diseases. Notably, therapeutic strategies to modulate fibrinogen levels have shown promise in experimental models of disease. Herein, we review pathways mediating fibrinogen synthesis, from gene expression to secretion. Knowledge of these mechanisms may lead to the identification of biomarkers and new therapeutic targets to modulate fibrinogen in health and disease.
血浆蛋白纤维蛋白原由 3 个结构基因（FGA、FGB 和 FGG）编码，这些基因转录成 mRNA，经过剪接和翻译，分别产生 3 条多肽链（Aα、Bβ和γ）。这些链被靶向分泌，经过翻译后修饰，并组装成六聚体“三聚体的二聚体”（AαBβγ）。完全组装的纤维蛋白原作为 340 kDa 的糖蛋白分泌到血液中。纤维蛋白原是血液中最常见的凝血蛋白之一，其表达受炎症细胞因子诱导，在急性炎症事件中，循环纤维蛋白原水平可能增加高达 3 倍。循环纤维蛋白原水平异常与出血和血栓形成障碍以及几种炎症性疾病有关。值得注意的是，调节纤维蛋白原水平的治疗策略在疾病的实验模型中显示出了前景。在此，我们综述了从基因表达到分泌介导纤维蛋白原合成的途径。对这些机制的了解可能会导致鉴定生物标志物和新的治疗靶点，以调节纤维蛋白原在健康和疾病中的水平。
