Cdc42-Interacting Protein 4 Represses E-Cadherin Expression by Promoting β-Catenin Translocation to the Nucleus in Murine Renal Tubular Epithelial Cells.

Renal fibrosis is an inevitable outcome of end-stage chronic kidney disease. During this process, epithelial cells lose E- cadherinexpression. β- Cateninmay act as a mediator by accumulation and translocation to the nucleus. Studies have suggested that CIP4, a Cdc42effector protein, is associated with β- catenin. However, whether CIP4 contributes to E- cadherinloss in epithelial cells by regulating β- catenintranslocation is unclear. In this study, we investigated the involvement of CIP4 in β- catenintranslocation. Expression of CIP4 was upregulated in renal tissues of 5/6 nephrectomized rats and mainly distributed in renal tubular epithelia. In TGF-β1-treated NRK-52E cells, upregulation of CIP4 expression was accompanied by reduced expression of E- cadherin. CIP4 overexpression promoted the translocation of β- cateninto the nucleus, which was accompanied by reduced expression of E- cadherineven without TGF-β1 stimulation. In contrast, CIP4 depletion by using siRNA inhibited the translocation of β- cateninto the nucleus and reversed the decrease in expression of E- cadherin. The interaction between CIP4 and β- cateninwas detected. We also show that β- catenindepletion could restore the expression of E- cadherinthat was suppressed by CIP4 overexpression. In conclusion, these results suggest that CIP4 overexpression represses E- cadherinexpression by promoting β- catenintranslocation to the nucleus.