Peroxidasin is regulated by the epithelial-mesenchymal transition master transcription factor Snai1

Abstract Peroxidasin (PXDN), an ECM protein with peroxidase activity, is integral to basement membrane consolidation through catalysis of sulfilimine bonds in collagen IV. PXDN is also involved in processes where epithelial-mesenchymal transition (EMT) takes place, namely fibrosis, development and cancer. We therefore investigated whether PXDN is regulated by the EMT-master-regulator, Snai1. During TGF-β1-induced EMT, PXDN expression decreased by up to 47% in two cervical-carcinoma cell lines, with concomitant increases in Snai1 and vimentin, and decrease in E-cadherin. TGF-β1 induced Snai1 binding to the PXDN promoter (as assessed by chromatin immunoprecipitation-PCR) and significantly repressed luciferase reporter gene expression, as did Snai1 overexpression. In summary, our findings show that Snai1 mediates repression of PXDN and consolidate a role for this ECM-modifier during EMT.