| First Author | Liu F | Year | 2011 |
| Journal | Diabetologia | Volume | 54 |
| Issue | 10 | Pages | 2713-23 |
| PubMed ID | 21744073 | Mgi Jnum | J:177093 |
| Mgi Id | MGI:5293595 | Doi | 10.1007/s00125-011-2237-y |
| Citation | Liu F, et al. (2011) C-reactive protein promotes diabetic kidney disease in a mouse model of type 1 diabetes. Diabetologia 54(10):2713-23 |
| abstractText | 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. |
