Background Transforming growth factor-β1 (TGF-β1) modulates multiple cellular functions during development and tissue homeostasis. A large amount of TGF-β1 is stored in platelet α-granules and released upon platelet activation. Whether platelet-derived TGF-β1 plays a role in venous thrombosis remains unclear. This study intends to assess the role of platelet-derived TGF-β1 in the development of venous thrombosis in mice. Material and Methods TGF-β1flox/flox and platelet-specific TGF-β1−/− mice were utilized to assess platelet function in vitro, arterial thrombosis induced by FeCl3, tail bleeding time, prothrombin time (PT), activated partial thromboplastin time (APTT), and deep vein thrombosis induced through ligation of the inferior vena cava (IVC). The IVC sample was collected to measure accumulation of neutrophils, monocytes, and the formation of neutrophil extracellular traps (NETs) by immunofluorescence staining. Results TGF-β1 deficiency in platelets did not affect the number of circulating platelets, platelet aggregation, adenosine triphosphate release, and integrin αIIbβ3 activation. Meanwhile, TGF-β1 deficiency did not alter the arterial thrombus formation, hemostasis, and coagulation time (PT and APTT), but significantly impaired venous thrombus formation, inhibited the recruitment and accumulation of neutrophils and monocytes in thrombi, as well as reduced formation of NETs and platelet-neutrophil complex. In addition, adoptive transfer of TGF-β1flox/flox platelets to TGF-β1−/− mice rescued the impaired venous thrombus formation, recruitment of leukocytes and monocytes, as well as the NETs formation. Conclusion In conclusion, platelet-derived TGF-β1 positively modulates venous thrombus formation in mice, indicating that targeting TGF-β1 might be a novel approach for treating venous thrombosis without increasing the risk of bleeding.

中文翻译：

---

血小板衍生的 TGF-β1 促进深静脉血栓形成

背景 转化生长因子-β1 (TGF-β1) 在发育和组织稳态过程中调节多种细胞功能。大量TGF-β1储存在血小板α颗粒中，并在血小板激活时释放。血小板衍生的 TGF-β1 是否在静脉血栓形成中发挥作用尚不清楚。本研究旨在评估血小板衍生的 TGF-β1 在小鼠静脉血栓形成中的作用。材料与方法 TGF-β1flox/flox 和血小板特异性 TGF-β1−/− 小鼠用于体外评估血小板功能、FeCl3 诱导的动脉血栓形成、尾部出血时间、凝血酶原时间（PT）、活化部分凝血活酶时间（APTT） ），以及通过结扎下腔静脉（IVC）引起的深静脉血栓。收集 IVC 样本，通过免疫荧光染色测量中性粒细胞、单核细胞的积累以及中性粒细胞胞外陷阱 (NET) 的形成。结果血小板中TGF-β1缺乏并不影响循环血小板数量、血小板聚集、三磷酸腺苷释放和整合素αIIbβ3激活。同时，TGF-β1缺乏并不改变动脉血栓形成、止血和凝血时间（PT和APTT），但显着损害静脉血栓形成，抑制血栓中中性粒细胞和单核细胞的募集和积累，并减少血栓形成。 NETs 和血小板-中性粒细胞复合物。此外，将 TGF-β1flox/flox 血小板过继转移至 TGF-β1−/− 小鼠可挽救受损的静脉血栓形成、白细胞和单核细胞的募集以及 NET 的形成。结论 总之，血小板源性 TGF-β1 正向调节小鼠静脉血栓形成，表明靶向 TGF-β1 可能是一种在不增加出血风险的情况下治疗静脉血栓形成的新方法。