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Diabetologia

Erschienen in:

01.10.2011 | Article

C-reactive protein promotes diabetic kidney disease in a mouse model of type 1 diabetes

verfasst von: F. Liu, H. Y. Chen, X. R. Huang, A. C. K. Chung, L. Zhou, P. Fu, A. J. Szalai, H. Y. Lan

Erschienen in: Diabetologia | Ausgabe 10/2011

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Abstract

Aims/hypothesis

Although C-reactive protein (CRP) has been implicated as a risk factor in diabetes, its pathogenic importance in diabetic kidney disease (DKD) remains unclear. The present study investigated the potential role of CRP in DKD.

Methods

Diabetes was induced by streptozotocin in human CRP transgenic and wild-type mice for assessment of kidney injury at 24 weeks by real-time PCR, immunohistochemistry and western blot analysis. In vitro, the pathogenic effect of CRP was investigated using human kidney tubular epithelial cells cultured with high glucose and/or CRP.

Results

We found that CRP transgenic mice developed much more severe diabetic kidney injury than wild-type mice, as indicated by a significant increase in urinary albumin excretion and kidney injury molecule-1 abundance, enhanced infiltration of macrophages and T cells, and upregulation of pro-inflammatory cytokines (IL-1β, TNFα) and extracellular matrix (collagen I, III and IV). Enhanced renal inflammation and fibrosis in CRP transgenic mice was associated with upregulation of CRP receptor, CD32a, and over-activation of the TGF-β/SMAD and nuclear factor κB signalling pathways. In vitro, CRP significantly upregulated pro-inflammatory cytokines (IL-1β, TNFα, monocyte chemoattractant protein-1 [MCP-1]) and pro-fibrotic growth factors (TGF-β1, connective tissue growth factor [CTGF]) via CD32a/64. CRP was induced by high glucose, which synergistically promoted high glucose-mediated renal inflammation and fibrosis.

Conclusions/interpretation

CRP is not only a biomarker, but also a mediator in DKD. Enhanced activation of TGF-β/SMAD and nuclear factor κB signalling pathways may be the mechanisms by which CRP promotes renal inflammation and fibrosis under diabetic conditions.

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Titel: C-reactive protein promotes diabetic kidney disease in a mouse model of type 1 diabetes
verfasst von: F. Liu
H. Y. Chen
X. R. Huang
A. C. K. Chung
L. Zhou
P. Fu
A. J. Szalai
H. Y. Lan
Publikationsdatum: 01.10.2011
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 10/2011
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-011-2237-y

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Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

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