Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Sci Rep. 2012;2:787. doi: 10.1038/srep00787. Epub 2012 Nov 9.
The coagulation/fibrinolysis system is essential for wound healing after vascular injury. According to the standard paradigm, the synthesis of most coagulation factors is restricted to liver, platelets and endothelium. We challenged this interpretation by measuring coagulation factors in nine human primary cell types. FX mRNA was expressed by fibroblasts, visceral preadipocytes/adipocytes and hepatocytes, but not in macrophages or other cells. All cells expressed FVIII except endothelial cells. Fibroblasts, endothelial cells and macrophages produced thrombomodulin but not FV. Interestingly, vascular-related cells (platelets/monocytes) that expressed FV did not express FX and vice versa. Monocytes expressed FV, FVIII and FXIIIA, which are positive regulators of clot formation, but these cells also contained thrombomodulin, a negative regulator of coagulation. Our data show that the expression of coagulation factors is much more complex than previously thought, and we speculate that this intricate regulation of coagulation factor expression is necessary for correct fine-tuning of fibrinogenesis versus fibrinolysis.
凝血/纤溶系统对于血管损伤后的伤口愈合至关重要。根据标准范式,大多数凝血因子的合成仅限于肝脏、血小板和内皮细胞。我们通过测量九种人类原代细胞类型中的凝血因子来挑战这一解释。FX mRNA 在成纤维细胞、内脏前脂肪细胞/脂肪细胞和肝细胞中表达,但在巨噬细胞或其他细胞中不表达。除了内皮细胞外,所有细胞都表达了 FVIII。成纤维细胞、内皮细胞和巨噬细胞产生血栓调节蛋白,但不产生 FV。有趣的是,表达 FV 的血管相关细胞(血小板/单核细胞)不表达 FX,反之亦然。单核细胞表达 FV、FVIII 和 FXIIIa,它们是血栓形成的正调节剂,但这些细胞也含有血栓调节蛋白,这是凝血的负调节剂。我们的数据表明,凝血因子的表达比以前认为的要复杂得多,我们推测这种复杂的凝血因子表达调控对于正确调整纤维蛋白生成与纤维蛋白溶解的平衡是必要的。