Binding of Hepatitis C Virus Envelope Protein E2 to CD81 Up-regulates Matrix Metalloproteinase-2 in Human Hepatic Stellate Cells

摘要: The hepatitis C virus (HCV) envelope E2 glycoprotein is a key molecule regulating the interaction of HCV with cell surface proteins. binds major extracellular loop human CD81, tetraspanin expressed on various types including hepatocytes and B lymphocytes. Regardless, information biological functions originating from this are largely unknown. Since hepatic stellate cells (HSC) express high levels CD81 at surface, we investigated E2/CD81 in HSC possible effects arising interaction. Matrix metalloproteinase-2 (MMP-2; gelatinase A), enzyme involved degradation normal matrix, was up-regulated following between CD81. In particular, by employing zymography Western blot, observed that binding to induces time-dependent increase synthesis activity MMP-2. This effect abolished preincubating an anti-CD81 neutralizing antibody. Similar were detected NIH3T3 mouse fibroblasts transfected identical time course features. addition, induced up-regulation MMP-2 increasing activator protein-2/DNA via ERK/MAPK phosphorylation. Finally, suppression RNA interference described these cells, indicating essential for activation signaling pathway leading These results suggest may represent potential target HCV. increased expression Increased matrix areas where concentrated favor inflammatory infiltration further parenchymal damage.