Mannan-binding lectin in diabetic kidney disease: the impact of mouse genetics in a type 1 diabetes model.

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-05-08 DOI:10.1155/2012/678381
Jakob Appel Østergaard, Mette Bjerre, Satish Posettihalli RamachandraRao, Kumar Sharma, Jens Randel Nyengaard, Troels Krarup Hansen, Steffen Thiel, Allan Flyvbjerg
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引用次数: 18

Abstract

Unlabelled: 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.

Results: 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.

Conclusions: Strain-specific MBL effects were found on downstream diabetic kidney changes. This emphasizes the importance of genetic background in this model of diabetic complications.

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甘露聚糖结合凝集素在糖尿病肾病中的作用:1型糖尿病模型中小鼠遗传学的影响
未标记的: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,它可以激活补体系统。血清MBL水平预测糖尿病患者后期肾功能损害。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,这种参与可能在不同的动物品系之间有所不同。因此,我们研究了遗传背景对MBL在糖尿病肾病中的作用的影响。材料/方法:比较C57BL/6JBomTac和129S6/SvEvTac小鼠。在这两个菌株中,用链脲佐菌素诱导野生型(WT)和mbl敲除型(MBL-KO)小鼠实验性1型糖尿病。以非糖尿病WT和MBL-KO小鼠为对照。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。结果:MBL加重糖尿病诱导的C57BL/6JBomTac小鼠肾脏生长和肾小球增大。MBL没有改变糖尿病对任何品系肾小球基底膜厚度或系膜体积的影响。糖尿病诱导的肾脏生长因子和基质成分基因转录的变化不受MBL的影响。结论:菌株特异性MBL对糖尿病下游肾脏的改变有影响。这强调了遗传背景在糖尿病并发症模型中的重要性。
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来源期刊
Experimental Diabetes Research
Experimental Diabetes Research 医学-内分泌学与代谢
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3-8 weeks
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