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Article: Downregulation of renal tubular Wnt/β-catenin signaling by Dickkopf-3 induces tubular cell death in proteinuric nephropathy

TitleDownregulation of renal tubular Wnt/β-catenin signaling by Dickkopf-3 induces tubular cell death in proteinuric nephropathy
Authors
Issue Date2016
Citation
Cell Death & Disease, 2016, v. 7, p. e2155 How to Cite?
AbstractStudies on the role of Wnt/beta-catenin signaling in different forms of kidney disease have yielded discrepant results. Here, we report the biphasic change of renal beta-catenin expression in mice with overload proteinuria in which beta-catenin was upregulated at the early stage (4 weeks after disease induction) but abrogated at the late phase (8 weeks). Acute albuminuria was observed at 1 week after bovine serum albumin injection, followed by partial remission at 4 weeks that coincided with overexpression of renal tubular beta-catenin. Interestingly, a rebound in albuminuria at 8 weeks was accompanied by downregulated tubular beta-catenin expression and heightened tubular apoptosis. In addition, there was an inverse relationship between Dickkopf-3 (Dkk-3) and renal tubular beta-catenin expression at these time points. In vitro, a similar trend in beta-catenin expression was observed in human kidney-2 (HK-2) cells with acute (upregulation) and prolonged (downregulation) exposure to albumin. Induction of a proapoptotic phenotype by albumin was significantly enhanced by silencing beta-catenin in HK-2 cells. Finally, Dkk-3 expression and secretion was increased after prolonged exposure to albumin, leading to the suppression of intracellular beta-catenin signaling pathway. The effect of Dkk-3 on beta-catenin signaling was confirmed by incubation with exogenous Dkk-3 in HK-2 cells. Taken together, these data suggest that downregulation of tubular beta-catenin signaling induced by Dkk-3 has a detrimental role in chronic proteinuria, partially through the increase in apoptosis.
Persistent Identifierhttp://hdl.handle.net/10722/227370

 

DC FieldValueLanguage
dc.contributor.authorWong, WLD-
dc.contributor.authorYiu, WH-
dc.contributor.authorWu, H-
dc.contributor.authorLi, R-
dc.contributor.authorLiu, Y-
dc.contributor.authorChan, KW-
dc.contributor.authorLeung, JCK-
dc.contributor.authorChan, YY-
dc.contributor.authorLai, KN-
dc.contributor.authorTang, SCW-
dc.date.accessioned2016-07-18T09:10:04Z-
dc.date.available2016-07-18T09:10:04Z-
dc.date.issued2016-
dc.identifier.citationCell Death & Disease, 2016, v. 7, p. e2155-
dc.identifier.urihttp://hdl.handle.net/10722/227370-
dc.description.abstractStudies on the role of Wnt/beta-catenin signaling in different forms of kidney disease have yielded discrepant results. Here, we report the biphasic change of renal beta-catenin expression in mice with overload proteinuria in which beta-catenin was upregulated at the early stage (4 weeks after disease induction) but abrogated at the late phase (8 weeks). Acute albuminuria was observed at 1 week after bovine serum albumin injection, followed by partial remission at 4 weeks that coincided with overexpression of renal tubular beta-catenin. Interestingly, a rebound in albuminuria at 8 weeks was accompanied by downregulated tubular beta-catenin expression and heightened tubular apoptosis. In addition, there was an inverse relationship between Dickkopf-3 (Dkk-3) and renal tubular beta-catenin expression at these time points. In vitro, a similar trend in beta-catenin expression was observed in human kidney-2 (HK-2) cells with acute (upregulation) and prolonged (downregulation) exposure to albumin. Induction of a proapoptotic phenotype by albumin was significantly enhanced by silencing beta-catenin in HK-2 cells. Finally, Dkk-3 expression and secretion was increased after prolonged exposure to albumin, leading to the suppression of intracellular beta-catenin signaling pathway. The effect of Dkk-3 on beta-catenin signaling was confirmed by incubation with exogenous Dkk-3 in HK-2 cells. Taken together, these data suggest that downregulation of tubular beta-catenin signaling induced by Dkk-3 has a detrimental role in chronic proteinuria, partially through the increase in apoptosis.-
dc.languageeng-
dc.relation.ispartofCell Death & Disease-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleDownregulation of renal tubular Wnt/β-catenin signaling by Dickkopf-3 induces tubular cell death in proteinuric nephropathy-
dc.typeArticle-
dc.identifier.emailYiu, WH: whyiu@hku.hk-
dc.identifier.emailLiu, Y: liuyang9@hku.hk-
dc.identifier.emailLeung, JCK: jckleung@hku.hk-
dc.identifier.emailChan, YY: yychanb@hku.hk-
dc.identifier.emailLai, KN: knlai@hku.hk-
dc.identifier.emailTang, SCW: scwtang@hku.hk-
dc.identifier.authorityLeung, JCK=rp00448-
dc.identifier.authorityLai, KN=rp00324-
dc.identifier.authorityTang, SCW=rp00480-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/cddis.2016.62-
dc.identifier.hkuros259636-
dc.identifier.volume7-
dc.identifier.spagee2155-
dc.identifier.epagee2155-

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