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.
Keywords: Cancer; Epithelial-mesenchymal transition; Fibrosis; Peroxidasin; Snai1; VPO1.
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