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Conference Paper: Activated Renal Tubular Wnt/β-Catenin Signaling Triggers Renal Inflammation during Proteinuria

TitleActivated Renal Tubular Wnt/β-Catenin Signaling Triggers Renal Inflammation during Proteinuria
Authors
Issue Date2017
PublisherAmerican Society of Nephrology. The Abstract's web site is located at https://www.asn-online.org/education/kidneyweek/archives/
Citation
American Society of Nephrology Kidney Week, New Orleans, USA, 31 October - 5 November 2017, In Journal of the American Society of Nephrology, 2017, v. 28 n. Abstract Suppl., p. 200 How to Cite?
AbstractBackground: Imbalance of Wnt/β-catenin signaling in renal cells is associated with renal dysfunction, yet the precise mechanism is poorly understood. Previously we observed activated Wnt/β-catenin signaling in renal tubules during proteinuric nephropathy with an unknown net effect (rescue vs. damage?) (Cell Death Dis 2016; 24;7:e2155). Methods: To identify the definitive role of tubular Wnt/β-catenin, we generated a novel transgenic “Tubcat” mouse, which conditionally expresses stabilized β-catenin specifically in renal tubules after tamoxifen administration. Results: Four weeks after tamoxifen induction, Tubcat mice displayed proteinuria and elevated BUN levels, implying a detrimental effect of the activated signaling. This was associated with tubulointerstitial infiltration predominantly by M1 macrophages and overexpression of the inflammatory chemocytokines CCL-2 and RANTES. Induction of overload proteinuria by low-endotoxin BSA injection for 4 weeks aggravated proteinuria and increased BUN levels to a significantly greater extent in Tubcat mice. Renal dysfunction correlated with the degree of M1 macrophage infiltration in the tubulointerstitium and renal cortical up-regulation of CCL-2, IL-17A, IL-1β, CXCL1 and ICAM-1. Finally, there was overexpression of cortical TLR-4 and NLRP-3 in Tubcat mice, irrespective of BSA injection. Conclusions: Conditional activation of renal tubular Wnt/β-catenin signaling enhances intrarenal inflammation via the TLR-4/NLRP-3 inflammasome axis in overload proteinuria. Funding support: National Natural Science Fund (NSFC) of China (grant no. 81570647)
DescriptionPoster presentation - Cell Signaling and Oxidative Stress - no. TH-PO388
Persistent Identifierhttp://hdl.handle.net/10722/259724
ISSN
2017 Impact Factor: 8.655
2015 SCImago Journal Rankings: 4.699

 

DC FieldValueLanguage
dc.contributor.authorWong, WLD-
dc.contributor.authorYiu, WH-
dc.contributor.authorChan, KW-
dc.contributor.authorLi, Y-
dc.contributor.authorLi, B-
dc.contributor.authorTaketo, MM-
dc.contributor.authorIgarashi, P-
dc.contributor.authorChan, YY-
dc.contributor.authorLeung, JCK-
dc.contributor.authorLai, KN-
dc.contributor.authorTang, SCW-
dc.date.accessioned2018-09-03T04:12:53Z-
dc.date.available2018-09-03T04:12:53Z-
dc.date.issued2017-
dc.identifier.citationAmerican Society of Nephrology Kidney Week, New Orleans, USA, 31 October - 5 November 2017, In Journal of the American Society of Nephrology, 2017, v. 28 n. Abstract Suppl., p. 200-
dc.identifier.issn1046-6673-
dc.identifier.urihttp://hdl.handle.net/10722/259724-
dc.descriptionPoster presentation - Cell Signaling and Oxidative Stress - no. TH-PO388-
dc.description.abstractBackground: Imbalance of Wnt/β-catenin signaling in renal cells is associated with renal dysfunction, yet the precise mechanism is poorly understood. Previously we observed activated Wnt/β-catenin signaling in renal tubules during proteinuric nephropathy with an unknown net effect (rescue vs. damage?) (Cell Death Dis 2016; 24;7:e2155). Methods: To identify the definitive role of tubular Wnt/β-catenin, we generated a novel transgenic “Tubcat” mouse, which conditionally expresses stabilized β-catenin specifically in renal tubules after tamoxifen administration. Results: Four weeks after tamoxifen induction, Tubcat mice displayed proteinuria and elevated BUN levels, implying a detrimental effect of the activated signaling. This was associated with tubulointerstitial infiltration predominantly by M1 macrophages and overexpression of the inflammatory chemocytokines CCL-2 and RANTES. Induction of overload proteinuria by low-endotoxin BSA injection for 4 weeks aggravated proteinuria and increased BUN levels to a significantly greater extent in Tubcat mice. Renal dysfunction correlated with the degree of M1 macrophage infiltration in the tubulointerstitium and renal cortical up-regulation of CCL-2, IL-17A, IL-1β, CXCL1 and ICAM-1. Finally, there was overexpression of cortical TLR-4 and NLRP-3 in Tubcat mice, irrespective of BSA injection. Conclusions: Conditional activation of renal tubular Wnt/β-catenin signaling enhances intrarenal inflammation via the TLR-4/NLRP-3 inflammasome axis in overload proteinuria. Funding support: National Natural Science Fund (NSFC) of China (grant no. 81570647)-
dc.languageeng-
dc.publisherAmerican Society of Nephrology. The Abstract's web site is located at https://www.asn-online.org/education/kidneyweek/archives/-
dc.relation.ispartofJournal of the American Society of Nephrology-
dc.relation.ispartofAmerican Society of Nephrology Kidney Week, 2017-
dc.titleActivated Renal Tubular Wnt/β-Catenin Signaling Triggers Renal Inflammation during Proteinuria-
dc.typeConference_Paper-
dc.identifier.emailYiu, WH: whyiu@hku.hk-
dc.identifier.emailChan, YY: yychanb@hku.hk-
dc.identifier.emailLeung, JCK: jckleung@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.identifier.hkuros288274-
dc.identifier.volume28-
dc.identifier.issueAbstract Suppl.-
dc.identifier.spage200-
dc.identifier.epage200-
dc.publisher.placeUnited States-

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