Exploring the mechanism of endothelial Pim-1 upregulation of tissue factor to initiate the hypercoagulable state in sepsis.

[BACKGROUND] During sepsis-induced coagulopathy (SIC), the balance of coagulation, anticoagulation, and fibrinolysis is disrupted, and endothelial dysfunction plays a key role in the disease progression. Current studies have indicated that the Proviral integration site for Moloney murine leukemia virus 1 (Pim-1) can promote thrombosis and activate an autoimmune response. This study aimed to assess the relevance of inhibiting Pim-1 as a potential therapeutic target for SIC.

[METHODS] Wild-type, Pim-1-KO, and TLR4-KO mice were categorized into the sham and cecal ligation and puncture (CLP) groups. Human umbilical vein endothelial cells were classified into the control, lipopolysaccharide (LPS) stimulation, and intervention groups. Enzyme-linked immunosorbent assay was used to detect plasma coagulation index in mice. Western blotting and immunofluorescence were employed to examine protein expression in tissues or cells. Additionally, immunohistochemistry and hematoxylin and eosin staining were conducted to detect liver/lung tissue damage. Tissue factor (TF) promoter activity was detected using a dual-luciferase reporter assay.

[RESULTS] Pim-1 kinase inhibition decreased the coagulation response of sepsis mice and improved the survival rate. Pim-1 activated the LPS-induced HUVECs downstream mTOR/Sp1 pathway, promoted TF activity. Pim-1 is mediated by the upstream TLR4 pathway to promote TF activity in LPS-induced HUVECs.

[CONCLUSIONS] Inhibiting the activity of Pim-1 kinase may be an effective way to improve the function of endothelial cells and treat SIC.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s10020-026-01433-4.