Østergaard Jakob Appel, Bjerre Mette, RamachandraRao Satish Posettihalli, Sharma Kumar, Nyengaard Jens Randel, Hansen Troels Krarup, Thiel Steffen, Flyvbjerg Allan
Department of Endocrinology and Internal Medicine, Aarhus University Hospital and The Medical Research Laboratories, Institute of Clinical Medicine, Faculty of Health Sciences, Aarhus University, 8000 Aarhus C, Denmark.
Exp Diabetes Res. 2012;2012:678381. doi: 10.1155/2012/678381. Epub 2012 May 8.
BACKGROUND. Mannan-binding lectin (MBL) is involved in the development of diabetic nephropathy. MBL is a part of the innate immune system where it can activate the complement system. Serum MBL level predicts later renal impairment in diabetes patients. Direct involvement of MBL in the development of diabetic kidney disease is observed in one animal strain. However, this involvement may differ among the animal strains. We thus examined the impact of the genetic background on the role of MBL in diabetic nephropathy.
MATERIALS/METHODS: C57BL/6JBomTac and 129S6/SvEvTac mice were compared. In both strains, experimental type 1 diabetes was induced in wild-type (WT) and MBL-knockout (MBL-KO) mice by streptozotocin. Nondiabetic WT and MBL-KO mice were used as controls. We tested if MBL modified the diabetes-induced kidney changes by two-way ANOVA allowing for interaction.
MBL aggravated diabetes-induced kidney growth and glomerulus enlargement in C57BL/6JBomTac mice. MBL did not modify diabetes effects on glomerular basement membrane thickness or mesangial volume in any strain. Diabetes-induced changes in renal gene transcription of growth factors and matrix components were unaffected by MBL.
Strain-specific MBL effects were found on downstream diabetic kidney changes. This emphasizes the importance of genetic background in this model of diabetic complications.
背景。甘露聚糖结合凝集素(MBL)参与糖尿病肾病的发展。MBL是先天免疫系统的一部分,在其中它可以激活补体系统。血清MBL水平可预测糖尿病患者后期的肾功能损害。在一种动物品系中观察到MBL直接参与糖尿病肾病的发展。然而,这种参与在不同动物品系中可能有所不同。因此,我们研究了遗传背景对MBL在糖尿病肾病中作用的影响。
材料/方法:比较了C57BL/6JBomTac和129S6/SvEvTac小鼠。在这两个品系中,通过链脲佐菌素在野生型(WT)和MBL基因敲除(MBL-KO)小鼠中诱导实验性1型糖尿病。非糖尿病的WT和MBL-KO小鼠用作对照。我们通过允许相互作用的双向方差分析测试了MBL是否改变了糖尿病诱导的肾脏变化。
在C57BL/6JBomTac小鼠中,MBL加剧了糖尿病诱导的肾脏生长和肾小球增大。在任何品系中,MBL均未改变糖尿病对肾小球基底膜厚度或系膜体积的影响。糖尿病诱导的生长因子和基质成分的肾脏基因转录变化不受MBL影响。
发现品系特异性的MBL对糖尿病肾脏下游变化有影响。这强调了遗传背景在这种糖尿病并发症模型中的重要性。