Upregulatory expression of furin and transforming growth factor-beta by fluid shear stress in vascular endothelial cells

Furin, a yeast Kex2-family endoprotease, converts many vasoregulatory prope ptides, including pro-transforming growth factor (TGF)-beta to their mature forms. We examined whether furin expression is regulated by shear stress i n vivo and in vitro. When an arteriovenous shunt was placed between the car otid artery and external jugular vein in rabbits, furin and TGF-beta were h ighly expressed in shear stress-loaded endothelial cells. Exposure of bovin e aortic endothelial cells in culture to shear stress induced furin and TGF -beta expression in a similar manner. Molecular analysis of furin expressio n in bovine aortic endothelial cells revealed that shear stress increases t he furin gene expression at transcriptional levels. Furthermore, TGF-beta i tself increased the furin mRNA levels. Shear-mediated furin expression was partly mediated by TGF-beta because shear-induced furin mRNA levels were co nsiderably decreased by overexpression of the truncated form of the TGF-bet a type II receptor. Likewise, blockade of furin activity by a furin inhibit or significantly decreased the endothelial production of mature TGF-beta. T aken together, the results indicate that furin expression is induced and ma intained by a coordination of shear stress and TGF-beta. Increased furin ex pression may facilitate the formation of mature TGF-beta, resulting in the enhanced effects of TGF-beta on endothelial cells and vascular smooth muscl e cells in the vasculature.