Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

• Published in: Diabetologia Vol. 50; no. 7; pp. 1541 - 1549
• Main Authors: Østergaard, J, Thiel, S, Gadjeva, M, Hansen, T. K, Rasch, R, Flyvbjerg, A
• Format: Journal Article
• Language: English
• Published: Berlin Berlin/Heidelberg : Springer-Verlag 01-07-2007; Springer; Springer Nature B.V
• Subjects: Albumin excretion; Albumins - metabolism; Animals; Associated diseases and complications; Biological and medical sciences; collagen; Collagen Type IV - biosynthesis; complement; Creatinine; Creatinine - urine; Diabetes; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Experimental - therapy; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - pathology; Diabetes. Impaired glucose tolerance; Diabetic angiopathy; Diabetic nephropathy; Drug dosages; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glucose; insulin-dependent diabetes mellitus; Ketamine; Kidney - pathology; Kidney diseases; Kidney weight; Kidneys; Laboratory animals; Lectins; Male; Mannose-binding lectin; Mannose-Binding Lectin - deficiency; Mannose-Binding Lectin - metabolism; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy; Nephrology. Urinary tract diseases; Organ Size; Pathogenesis; Streptozocin - pharmacology; Urinary system involvement in other diseases. Miscellaneous; Urine; Vascular endothelial growth factor; Denmark; United States > US; Germany; Aarhus Denmark; Endocrinopathy; Diabetic angiopathy, Diabetic nephropathy; Kidney weight, Mannose-binding lectin; Autoimmune disease; Mannose; Complement; Diabetic nephropathy; Streptozotocin; Kidney disease; Immunopathology; Excretion; Urinary system disease; Deficiency; Glycoprotein; Rodentia; Albumin; Albumin excretion; Concomitant disease; Vertebrata; Mammalia; Mouse; Type 1 diabetes; Animal; Collagen; Models
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-007-0686-0

Aims/hypothesis An increasing amount of evidence indicates that mannose-binding lectin (MBL) plays a role in the development of diabetic nephropathy. The main objective of the study was to analyse whether MBL influences the effects of diabetes on the kidneys. Materials and methods In one group of wild-type mice and in one group of MBL double knockout mice we induced diabetes by the use of streptozotocin as a model of type 1 diabetes. Two groups of non-diabetic mice, wild-type and MBL knockout, were also included. By two-way ANOVA we evaluated if MBL modulated the effects of diabetes by testing the interaction between diabetes and MBL. Results MBL interacted with the effects of diabetes on three outcome measures: kidney weight (p < 0.001), urinary albumin excretion (p = 0.001) and the expression of collagen IVα1 (Col4a1) mRNA (p = 0.002). This means that the effects that diabetes normally has on these parameters were significantly modified by MBL. MBL showed a tendency to interact with the effects of diabetes on glomerular basement membrane thickness and total mesangial volume (p = 0.065 and p = 0.063, respectively). Glomerular volume and total mesangial volume were significantly smaller in animals lacking MBL than in wild-type animals (p = 0.006 and p = 0.047, respectively). Conclusions/interpretation These findings, for the first time, show that the degree of kidney alteration as a consequence of diabetes is modified by MBL. These findings support a pivotal role of MBL in the development of diabetic kidney disease.