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

Authors

Hyunjae Chung, University of Calgary
Rithwik Ramachandran, University of Calgary
Morley D. Hollenberg, University of Calgary
Daniel A. Muruve, University of Calgary

Document Type

Article

Publication Date

12-27-2013

Journal

Journal of Biological Chemistry

Volume

288

Issue

52

First Page

37319

Last Page

37331

URL with Digital Object Identifier

10.1074/jbc.M113.492793

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.