Title : DNA hypermethylation of sFRP5 contributes to indoxyl sulfate-induced renal fibrosis.

Pub. Date : 2017 Jun

PMID : 28508124






5 Functional Relationships(s)
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1 DNA hypermethylation of sFRP5 contributes to indoxyl sulfate-induced renal fibrosis. Indican secreted frizzled related protein 5 Homo sapiens
2 In vitro investigations in human renal tubular HK-2 cells revealed that indoxyl sulfate exhibited a potent ability to induce Wnt/beta-catenin activation through the downregulation of sFRP5, a gene that codes for an extracellular antagonist of Wnt signaling, by increasing the DNA methylation level of its promoter CpG islands. Indican secreted frizzled related protein 5 Homo sapiens
3 The increased expression of DNA methyltransferases following the activation of ROS/ERK1/2 signaling was responsible for the DNA hypermethylation of sFRP5 induced by indoxyl sulfate. Indican secreted frizzled related protein 5 Homo sapiens
4 Conversely, treatment with 5-aza-2"-deoxycytidine, an inhibitor of DNA methyltransferases, significantly reduced indoxyl sulfate-induced sFRP5 downregulation and Wnt/beta-catenin activation. Indican secreted frizzled related protein 5 Homo sapiens
5 Our results suggest that indoxyl sulfate promotes renal fibrosis through the induction of DNA hypermethylation of sFRP5, and thereafter the activation of Wnt/beta-catenin signaling. Indican secreted frizzled related protein 5 Homo sapiens