Proteinase-activated receptor-2 transactivation of epidermal growth factor receptor and transforming growth factor-β receptor signaling pathways contributes to renal fibrosis

Abstract

Background: The role for proteinase-activated receptor (PAR)-2 in the pathogenesis of renal fibrosis is not previously described. Results: PAR2 -/- mice displayed attenuated renal fibrosis in vivo. PAR2 transactivation of EGF and TGFβ receptor signaling pathways induced Smad2 phosphorylation and connective tissue growth factor gene expression. Conclusion: PAR2 activation results in profibrotic signaling and gene expression. Significance: PAR2 represents a potential therapeutic target for chronic kidney disease. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.