2. Academic Validation
  3. FGF1 attenuates sepsis-induced coagulation dysfunction and hepatic injury via IL6/STAT3 pathway inhibition

FGF1 attenuates sepsis-induced coagulation dysfunction and hepatic injury via IL6/STAT3 pathway inhibition

  • Biochim Biophys Acta Mol Basis Dis. 2024 Jun 11;1870(7):167281. doi: 10.1016/j.bbadis.2024.167281.
Jianing Bi 1,  Yanjing Wang 2,  Kaicheng Wang 3,  Yuanyuan Sun 3,  Fanrong Ye 4,  Xiaojie Wang 5,  Jingye Pan 6
Affiliations

Affiliations

  • 1 Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Zhejiang Key Laboratory of Critical Care Medicine, Wenzhou, China; Wenzhou Key Laboratory of Critical Care and Artificial Intelligence, Wenzhou, China; School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China. Electronic address: bijianing@wmu.edu.cn.
  • 2 School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
  • 3 Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Zhejiang Key Laboratory of Critical Care Medicine, Wenzhou, China; Wenzhou Key Laboratory of Critical Care and Artificial Intelligence, Wenzhou, China.
  • 4 Departments of Nuclear Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 5 School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China. Electronic address: 18858811123@126.com.
  • 6 Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Zhejiang Key Laboratory of Critical Care Medicine, Wenzhou, China; Wenzhou Key Laboratory of Critical Care and Artificial Intelligence, Wenzhou, China. Electronic address: wmupanjingye@126.com.
PMID: 38870868 DOI: 10.1016/j.bbadis.2024.167281
Abstract

Background & aims: Sepsis, a globally prevalent and highly lethal condition, remains a critical medical challenge. This investigation aims to assess the relevance of FGF1 as a potential therapeutic target for sepsis.

Methods: Sepsis was induced in C57BL/6 mice through LPS administration to establish an in vivo animal model. Various in vitro assays were conducted using human umbilical vein endothelial cells to elucidate the role of FGF1 in the disruption of the coagulation system and liver injury associated with sepsis, as well as to explore its underlying molecular mechanisms.

Results: In in vivo experiments, FGF1 ameliorated coagulation system disruption in septic mice by reducing the levels of pro-inflammatory and coagulation-related factors in the bloodstream. FGF1 also enhanced liver function in septic mice, mitigating liver inflammation and cell Apoptosis, fostering liver vascular regeneration, increasing liver blood perfusion, and improving mouse survival. In vitro experiments demonstrated that FGF1 could inhibit LPS-induced inflammatory responses and Apoptosis in endothelial cells, fortify endothelial cell barrier function, decrease endothelial cell permeability, promote endothelial cell proliferation, and restore endothelial cell tube-forming ability. Both in vivo and in vitro experiments substantiated that FGF1 improved sepsis by inhibiting the IL-6/STAT3 signaling pathway.

Conclusion: In summary, our study indicates that FGF1 mitigates excessive inflammatory responses in sepsis by suppressing the IL-6/STAT3 signaling pathway, thereby improving systemic blood circulation and ameliorating liver damage in septic organisms. Consequently, this research identifies FGF1 as a potential clinical target for the treatment of human sepsis.

Keywords

Disseminated intravascular coagulation; FGF1; IL-6/STAT3 signaling pathway; LPS; Sepsis.

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