F Wu Email & Phone Number

Major Academic FindingsVascular leakage is involved in the pathogenesis of lung permeability and tumor metastasis. Syndecan-1 is the protein backbone of glycocalyx lining the vascular endothelium and maintaining the endothelial integrity. We found for the first time that fibrinogen, the major component of plasma, binds with syndecan-1 to exert the protective effects on the lung endothelial integrity in mice after trauma/bacterial pneumonia. Fibrinogen binding to heparan sulfate on syndecan-1/glycocalyx forms a gel-like layer that lines the endothelium and maintains vascular barrier integrity. 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/hemorrhage 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.1. Fibrinogen protects vascular integrity and prevents lung injury.Wu et al. Fibrinogen inhibits metalloproteinase-9 activation and syndecan-1 cleavage to protect lung function in ApoE null mice after hemorrhagic shock. J Surg Res 2023; 288:208-214.Wu et al. Fibrinogen protects against barrier dysfunction through maintaining cell surface syndecan-1 in vitro. Shock. 2019; 51:740-744. 2. Anti-miR-19b oligos protect the lungs in mice after hemorrhage shock.Wu et al. miR-19b targets pulmonary endothelial syndecan-1 following hemorrhagic shock. Sci Rep. 2020; 10:15811.3. 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.

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  Western University

  Physiology And Pharmacology