PMID- 21744073
OWN - NLM
STAT- MEDLINE
DCOM- 20120424
LR  - 20220321
IS  - 1432-0428 (Electronic)
IS  - 0012-186X (Linking)
VI  - 54
IP  - 10
DP  - 2011 Oct
TI  - C-reactive protein promotes diabetic kidney disease in a mouse model of type 1 
      diabetes.
PG  - 2713-23
LID - 10.1007/s00125-011-2237-y [doi]
AB  - 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-1beta, TNFalpha) 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-beta/SMAD and nuclear factor kappaB signalling pathways. In vitro, CRP significantly 
      upregulated pro-inflammatory cytokines (IL-1beta, TNFalpha, monocyte chemoattractant 
      protein-1 [MCP-1]) and pro-fibrotic growth factors (TGF-beta1, 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-beta/SMAD and nuclear factor kappaB signalling pathways 
      may be the mechanisms by which CRP promotes renal inflammation and fibrosis under 
      diabetic conditions.
FAU - Liu, F
AU  - Liu F
AD  - Department of Nephrology, West China Hospital of Sichuan University, Chengdu, 
      People's Republic of China.
FAU - Chen, H Y
AU  - Chen HY
FAU - Huang, X R
AU  - Huang XR
FAU - Chung, A C K
AU  - Chung AC
FAU - Zhou, L
AU  - Zhou L
FAU - Fu, P
AU  - Fu P
FAU - Szalai, A J
AU  - Szalai AJ
FAU - Lan, H Y
AU  - Lan HY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110709
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - C-Reactive Protein/genetics/*metabolism
MH  - Cell Line
MH  - Chemokine CCL2/metabolism
MH  - Connective Tissue Growth Factor/metabolism
MH  - Diabetes Mellitus, Type 1/genetics/*metabolism
MH  - Diabetic Nephropathies/*metabolism
MH  - Immunohistochemistry
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - NF-kappa B/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Transforming Growth Factor beta1/metabolism
EDAT- 2011/07/12 06:00
MHDA- 2012/04/25 06:00
CRDT- 2011/07/12 06:00
PHST- 2011/01/04 00:00 [received]
PHST- 2011/06/08 00:00 [accepted]
PHST- 2011/07/12 06:00 [entrez]
PHST- 2011/07/12 06:00 [pubmed]
PHST- 2012/04/25 06:00 [medline]
AID - 10.1007/s00125-011-2237-y [doi]
PST - ppublish
SO  - Diabetologia. 2011 Oct;54(10):2713-23. doi: 10.1007/s00125-011-2237-y. Epub 2011 
      Jul 9.