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

Diabetologia. 2007 Jul;50(7):1541-9. doi: 10.1007/s00125-007-0686-0. Epub 2007 May 1.

Abstract

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 IV alpha 1 (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / metabolism
  • Animals
  • Collagen Type IV / biosynthesis
  • Creatinine / urine
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy*
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / pathology*
  • Female
  • Kidney / pathology*
  • Male
  • Mannose-Binding Lectin / deficiency*
  • Mannose-Binding Lectin / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Size
  • Streptozocin / pharmacology*

Substances

  • Albumins
  • Collagen Type IV
  • Mannose-Binding Lectin
  • Streptozocin
  • Creatinine