Abstract
AimsTo investigate if nuclear NF-κB p65 expression in ex vivo isolated peripheral blood mononuclear cells correlates with urinary MCP-1 or RANTES and the severity of type 2 diabetic nephropathy.MethodsAccording to their urinary albumin-to-creatinine ratio (uACR), 107 patients with type 2 diabetes (eGFR >60 ml/min) were divided into normal albuminuria group (DN0 group, 38 cases), microalbuminuria group (DN1 group, 38 cases), and macroalbuminuria group (DN2 group, 31 cases), compared with matched healthy normal control group (NC group, 30 cases). Nuclear NF-κB p65 protein expression levels in peripheral blood mononuclear cells were detected by western blotting. Real-time quantitative polymerase chain reaction was used to detect NF-κB p65 mRNA expression and ELISA assay was used to detect the levels of urinary MCP-1 and RANTES.ResultsNuclear NF-κB p65 protein and NF-κB p65 mRNA expression levels in peripheral blood mononuclear cells, urinary MCP-1/Cr and RANTES/Cr were all significantly higher in all diabetes groups as compared with NC group. In particular, the increase of nuclear NF-κB p65 protein and NF-κB p65 mRNA expressions, urinary MCP-1/Cr and RANTES/Cr all correlated with the severity of type 2 diabetic nephropathy as indicated by the increase in uACR. Pearson correlation analysis indicated that both urinary MCP-1/Cr and RANTES/Cr were positively correlated with nuclear NF-κB p65 protein or NF-κB p65 mRNA levels. Stepwise multiple regression analysis showed that nuclear NF-κB p65 protein or NF-κB p65 mRNA was an independent variable for urinary MCP-1/Cr, and MCP-1/Cr and RANTES/Cr were two independent variables for uACR.ConclusionOur research demonstrates that nuclear NF-κB p65 protein and mRNA expressions in ex vivo isolated peripheral blood mononuclear cells well correlate with urinary MCP-1/Cr, RANTES/Cr and the severity of type 2 diabetic nephropathy.
Highlights
Diabetic nephropathy (DN) is one of the many severe microvascular complications of diabetes
The Estimated glomerular filtration rate (eGFR) level was significantly lower in DN2 group compared to NC, DN0 or DN1 groups, but there was no significant difference between NC, DN0 and DN1 groups
We have found that both the nuclear protein and mRNA levels of peripheral blood mononuclear cell NF-kB p65 were higher in all diabetes groups than the control group, and were gradually elevated with the progression of type 2 diabetic nephropathy as indicated by the increase of urinary albumin-to-creatinine ratio (uACR) and proceeded to a peak expression in the macroalbuminuria group
Summary
Diabetic nephropathy (DN) is one of the many severe microvascular complications of diabetes. High glucose, advanced glycosylation end products, angiotensin II and other pathogenic factors for DN can all activate NF-kB pathway in mesangial cells and renal tubular epithelial cells, and regulate the transcription and synthesis of MCP-1 and RANTES [10,11]. Little research has been done on the relationship between nuclear NF-kB expression in peripheral blood mononuclear cells, as a marker for activation of NF-kB signaling pathway, and MCP-1 and RANTES levels. We determined peripheral blood mononuclear cells nuclear NF-kB p65 protein and NF-kB p65 mRNA expressions, and urinary chemokine MCP-1 and RANTES levels in patients with type 2 diabetes and matched healthy controls. We further investigated the correlation between nuclear NF-kB p65 protein, NF-kB p65 mRNA levels and the severity of type 2 diabetic nephropathy
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