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01.01.2012 | Article

Implication of dysregulation of the canonical wingless-type MMTV integration site (WNT) pathway in diabetic nephropathy

verfasst von: T. Zhou, X. He, R. Cheng, B. Zhang, R. R. Zhang, Y. Chen, Y. Takahashi, A. R. Murray, K. Lee, G. Gao, J-x. Ma

Erschienen in: Diabetologia | Ausgabe 1/2012

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Abstract

Aims/hypothesis

The wingless-type MMTV integration site (WNT) pathway mediates multiple physiological and pathological processes, such as inflammation, angiogenesis and fibrosis. The aim of this study was to investigate whether canonical WNT signalling plays a role in the pathogenesis of diabetic nephropathy.

Methods

Expression of WNT ligands and frizzled receptors in the canonical WNT pathway in the kidney was compared at the mRNA level using real-time RT-PCR between Akita mice, streptozotocin-induced diabetic rats and db/db mice and their respective non-diabetic controls. Renal function was evaluated by measuring the urine albumin excretion. Human renal proximal tubular epithelial cells were treated with high-glucose medium and 4-hydroxynonenal (HNE). Levels of β-catenin, connective tissue growth factor and fibronectin were determined by western blot analysis.

Results

Some of the WNT ligands and frizzled receptors showed increased mRNA levels in the kidneys of Akita mice, streptozotocin-induced diabetic rats and db/db mice compared with their non-diabetic controls. Renal levels of β-catenin and WNT proteins were upregulated in these diabetic models. Lowering the blood glucose levels by insulin attenuated the activation of WNT signalling in the kidneys of Akita mice. In cultured human renal proximal tubular epithelial cells, both high glucose and HNE activated WNT signalling. Inhibition of WNT signalling with a monoclonal antibody blocking LDL-receptor-related protein 6 ameliorated renal inflammation and fibrosis and reduced proteinuria in Akita mice.

Conclusions/interpretation

The WNT pathway is activated in the kidneys of models of both type 1 and 2 diabetes. Dysregulation of the WNT pathway in diabetes represents a new pathogenic mechanism of diabetic nephropathy and renders a new therapeutic target.

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Titel: Implication of dysregulation of the canonical wingless-type MMTV integration site (WNT) pathway in diabetic nephropathy
verfasst von: T. Zhou
X. He
R. Cheng
B. Zhang
R. R. Zhang
Y. Chen
Y. Takahashi
A. R. Murray
K. Lee
G. Gao
J-x. Ma
Publikationsdatum: 01.01.2012
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 1/2012
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-011-2314-2

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Implication of dysregulation of the canonical wingless-type MMTV integration site (WNT) pathway in diabetic nephropathy

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

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Parodontalbehandlung verbessert Prognose bei Katheterablation

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Denken Sie bei starker Blutung auch an die Hemmkörper-Hämophilie

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

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Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

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