title: C-reactive protein promotes diabetic kidney disease in a mouse model of type 1 diabetes.
abstract: OBJECTIVE
  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
  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.
authors: Department of Nephrology, West China Hospital of Sichuan University, Chengdu, People's Republic of China.
authors: F
authors: F
authors: Liu
authors: H Y
authors: HY
authors: Chen
authors: X R
authors: XR
authors: Huang
authors: A C K
authors: AC
authors: Chung
authors: L
authors: L
authors: Zhou
authors: P
authors: P
authors: Fu
authors: A J
authors: AJ
authors: Szalai
authors: H Y
authors: HY
authors: Lan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D002097:C-Reactive Protein