Krüppel-like factors (KLFs) play essential roles in multiple biological functions, including maintaining vascular homeostasis. KLF11, a causative gene for maturity-onset diabetes of the young type 7, inhibits endothelial activation and protects against stroke. However, the role of KLF11 in venous thrombosis remains to be explored. Utilizing stasis-induced murine deep vein thrombosis (DVT) model and cultured endothelial cells (ECs), we identified an increase of KLF11 expression under prothrombotic conditions both in vivo and in vitro. The expression change of thrombosis-related genes was determined by utilizing gain- and loss-of-function approaches to alter KLF11 expression in ECs. Among these genes, KLF11 significantly downregulated tumor necrosis factor-α (TNF-α)-induced tissue factor (TF) gene transcription. Using reporter gene assay, chromatin immunoprecipitation assay, and co-immunoprecipitation, we revealed that KLF11 could reduce TNF-α-induced binding of early growth response 1 (EGR1) to TF gene promoter in ECs. In addition, we demonstrated that conventional Klf11 knockout mice were more susceptible to developing stasis-induced DVT. These results suggest that under prothrombotic conditions, KLF11 downregulates TF gene transcription via inhibition of EGR1 in ECs. In conclusion, KLF11 protects against venous thrombosis, constituting a potential molecular target for treating thrombosis.

Krüppel 样因子 (KLF) 在多种生物功能中发挥着重要作用，包括维持血管稳态。KLF11 是年轻 7 型成年发病糖尿病的致病基因，可抑制内皮激活并预防中风。然而，KLF11 在静脉血栓形成中的作用仍有待探讨。利用瘀滞诱导的小鼠深静脉血栓 (DVT) 模型和培养的内皮细胞 (EC)，我们在体内和体外均发现在血栓前条件下 KLF11 表达增加。通过利用功能获得和丧失功能的方法改变 EC 中 KLF11 的表达来确定血栓形成相关基因的表达变化。在这些基因中，KLF11 显着下调肿瘤坏死因子-α (TNF-α) 诱导的组织因子 ( TF ) 基因转录。通过报告基因测定、染色质免疫沉淀测定和免疫共沉淀，我们发现 KLF11 可以减少 TNF-α 诱导的早期生长反应 1 (EGR1) 与 EC 中TF 基因启动子的结合。此外，我们证明传统的Klf11敲除小鼠更容易发生停滞诱导的 DVT。这些结果表明，在促血栓条件下，KLF11 通过抑制 EC 中的 EGR1 来下调TF基因转录。总之，KLF11 可预防静脉血栓形成，构成治疗血栓形成的潜在分子靶点。