Feng Wu, PhD

University of Western Ontario, PhD, Phyiology.

Vascular leakage is involved in the pathogenesis of lung injury and tumor metastasis. We found that fibrinogen binding to heparan sulfate on syndecan-1/glycocalyx forms a gel-like layer that lines the endothelium and maintains endothelial barrier. This gel-like layer shields the cleavage sites on syndecan-1/glycocalyx by MMP9, which otherwise cleaves syndecan-1/glycocalyx to cause lung vascular leakage. It is known that fibrinogen is oxidized in human trauma/pneumonia patients. Our study suggests that maintaining fibrinogen in reduced state and/or inhibiting MMP9 activity could provide a therapy for the lung injury in trauma/pneumonia patients. Since the ischemia after trauma resembles the hypoxia microenvironment promoting tumor growth, maintaining fibrinogen in reduced state and/or inhibiting MMP9 activity could also be used to treating tumor metastasis through stabilizing the endothelial integrity.

Septic shock, hemorrhage shock, acute lung injury, vascular leakage, endothelial barrier dysfunction, stress fibers, antioxidants, syndecan-1, fibrinogen, miR-19b,

1. Fibrinogen protects vascular integrity and prevents lung injury.
Wu et al. Fibrinogen based resuscitation mitigates lung injury in mice with bacterial pneumonia after hemorrhagic shock. Biochem Biophys Rep. 2025; 42:102054.

2. Vitamin C intravenous injection increases survival in polymicrobial sepsis.
Wu et al. Ascorbate protects against impaired arteriolar constriction in sepsis by inhibiting iNOS expression. Free Radic Biol Med. 2004; 37:1282-1289.