Abstract by Phil Smit
Chemistry and Biochemistry
Furin Inhibition: A Potential Treatment for Liver Fibrosis
Transforming Growth Factor β (TGF-β), an inflammatory cytokine, has been shown to directly upregulate fibrosis in the extra cellular matrix (ECM), leading to elevated ECM remodeling, or fibrosis, by activating matrix metalloproteases (MMPs). Other groups showed that Furin processes inactive proTGF-β, transforming it into TGF-β. Nelfinavir and Darunavir are FDA approved protease inhibitors used to treat HIV, and our lab has shown they can be used to inhibit Furin to treat anemia. No data exists to show that these drugs inhibit Furin to treat fibrosis. Our goals are to demonstrate that Furin inhibition can block TGF-β and MMP activation. This could be a potential treatment for lung and liver fibrosis. Data will be presented to show inhibition of pro-MMP-14, pro-TGF-B and Pro-hepcidin activation by Nelfinavir.