| Autor: |
Dørflinger GH; Medical/Steno Aarhus Research Laboratory, Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark.; Department of Internal Medicine, Regional Hospital Gødstrup, 7400 Herning, Denmark., Holt CB; Medical/Steno Aarhus Research Laboratory, Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark.; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark., Thiel S; Department of Biomedicine, Aarhus University, 8200 Aarhus, Denmark., Bech JN; Department of Internal Medicine, Regional Hospital Gødstrup, 7400 Herning, Denmark.; University Clinic in Nephrology and Hypertension, Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark., Østergaard JA; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark.; Steno Diabetes Center Aarhus, 8200 Aarhus, Denmark., Bjerre M; Medical/Steno Aarhus Research Laboratory, Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark. |
| Abstrakt: |
Autoreactivity of the complement system may escalate the development of diabetic nephropathy. We used the BTBR OB mouse model of type 2 diabetes to investigate the role of the complement factor mannan-binding lectin (MBL) in diabetic nephropathy. Female BTBR OB mice ( n = 30) and BTBR non-diabetic WT mice ( n = 30) were included. Plasma samples (weeks 12 and 21) and urine samples (week 19) were analyzed for MBL, C3, C3-fragments, SAA3, and markers for renal function. Renal tissue sections were analyzed for fibrosis, inflammation, and complement deposition. The renal cortex was analyzed for gene expression (complement, inflammation, and fibrosis), and isolated glomerular cells were investigated for MBL protein. Human vascular endothelial cells cultured under normo- and hyperglycemic conditions were analyzed by flow cytometry. We found that the OB mice had elevated plasma and urine concentrations of MBL-C ( p < 0.0001 and p < 0.001, respectively) and higher plasma C3 levels ( p < 0.001) compared to WT mice. Renal cryosections from OB mice showed increased MBL-C and C4 deposition in the glomeruli and increased macrophage infiltration ( p = 0.002). Isolated glomeruli revealed significantly higher MBL protein levels ( p < 0.001) compared to the OB and WT mice, and no renal MBL expression was detected. We report that chronic inflammation plays an important role in the development of DN through the binding of MBL to hyperglycemia-exposed renal cells. |
