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

TitleC-reactive protein promotes diabetic kidney disease in a mouse model of type 1 diabetes
Authors
KeywordsNF-κB
TGF-β/SMAD
Fibrosis
Inflammation
Diabetic nephropathy
CRP
Issue Date2011
Citation
Diabetologia, 2011, v. 54, n. 10, p. 2713-2723 How to Cite?
AbstractAims/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. © 2011 Springer-Verlag.
Persistent Identifierhttp://hdl.handle.net/10722/199913
ISSN
2015 Impact Factor: 6.206
2015 SCImago Journal Rankings: 3.528
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, Fei-
dc.contributor.authorChen, Hai-Yong-
dc.contributor.authorHuang, Xiaoru-
dc.contributor.authorChung, Arthur Chi Kong-
dc.contributor.authorZhou, Li-
dc.contributor.authorFu, Ping-
dc.contributor.authorSzalai, Alexander J.-
dc.contributor.authorLan, Huiyao-
dc.date.accessioned2014-07-26T23:10:54Z-
dc.date.available2014-07-26T23:10:54Z-
dc.date.issued2011-
dc.identifier.citationDiabetologia, 2011, v. 54, n. 10, p. 2713-2723-
dc.identifier.issn0012-186X-
dc.identifier.urihttp://hdl.handle.net/10722/199913-
dc.description.abstractAims/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. © 2011 Springer-Verlag.-
dc.languageeng-
dc.relation.ispartofDiabetologia-
dc.subjectNF-κB-
dc.subjectTGF-β/SMAD-
dc.subjectFibrosis-
dc.subjectInflammation-
dc.subjectDiabetic nephropathy-
dc.subjectCRP-
dc.titleC-reactive protein promotes diabetic kidney disease in a mouse model of type 1 diabetes-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s00125-011-2237-y-
dc.identifier.pmid21744073-
dc.identifier.scopuseid_2-s2.0-80054116064-
dc.identifier.hkuros232097-
dc.identifier.volume54-
dc.identifier.issue10-
dc.identifier.spage2713-
dc.identifier.epage2723-
dc.identifier.eissn1432-0428-
dc.identifier.isiWOS:000294683000027-

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