Journal of inflammation research
KLF4 Protects Against Sepsis-Induced Coagulopathy via Inhibition of the AKT/mTOR/STAT3 Signaling Pathway
By Zhang R, Hong Y, Hai D and 8 others.
Abstract
Purpose
Coagulation dysfunction is an independent predictor of morbidity and mortality in patients with severe sepsis, yet current therapeutic options remain inadequate. This study systematically evaluated the therapeutic potential of Krüppel-like factor 4 (KLF4) in sepsis-induced coagulopathy and explored the underlying molecular mechanisms.
Methods
In vivo, mice were randomized into sham operation group, cecal ligation and puncture (CLP) group, and CLP + APTO-253 groups. The KLF4 agonist APTO-253 was intraperitoneally administered to CLP-induced septic mice to evaluate systemic inflammation, coagulation dysfunction, acute lung injury, and survival outcomes. In vitro, RAW264.7 macrophages were assigned to six core treatment groups: control group, APTO-253 group, LPS group, LPS + APTO-253 group, LPS + KLF4 overexpression group, and LPS + KLF4 knockdown group. Cellular inflammatory responses, coagulation-related biomarkers, and AKT/mTOR/STAT3 pathway activity were detected.