Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
Nephrol Dial Transplant. 2011 Jul;26(7):2153-60. doi: 10.1093/ndt/gfq708. Epub 2010 Nov 22.
GeneChip Expression Analysis was employed to survey the glomerular gene expression profile in a type 2 diabetes (T2D) model of KK/Ta mice fed with a high-calorie diet (HC), and we focused on the role of mindin (also called spondin 2), whose expression is upregulated by HC.
Isolated glomeruli from three 20-week-old KK/Ta mice fed with HC or a standard diet (SD) were dissected. Total RNA was extracted and labelled for hybridization using the Affymetrix GeneChip Mouse Genome 430 2.0 Array. The gene expression profile was compared between the HC and SD groups using GeneSpring 7.3.1 software. Mindin expression was examined using real-time PCR, western blot analysis and immunohistochemical staining in the glomeruli, cultured podocytes and urine samples of both mice and humans.
Podocyte foot process effacement was observed in mice fed with HC. The mindin protein expression levels in mice were localized in the podocytes, and their levels in the glomeruli were increased in the HC group compared with the SD group. The levels of urinary mindin in the HC group at 16 weeks of age were also significantly higher than those in the SD group although albumin/creatinine ratio (ACR) did not differ between the groups. Furthermore, the levels in patients with T2D were higher than those in healthy individuals and increased gradually with increases in ACR.
Mindin could be related to podocyte injury and appears to be an early biomarker of the progression of diabetic nephropathy.
我们采用基因芯片表达分析技术，研究了高热量饮食喂养的 2 型糖尿病（T2D）KK/Ta 小鼠模型的肾小球基因表达谱，并重点关注 mindin（也称为 spondin 2）的作用，其表达受 HC 上调。
从喂食高热量饮食（HC）或标准饮食（SD）的 3 只 20 周龄 KK/Ta 小鼠中分离出肾小球。提取总 RNA 并使用 Affymetrix GeneChip Mouse Genome 430 2.0 Array 进行杂交标记。使用 GeneSpring 7.3.1 软件比较 HC 和 SD 组之间的基因表达谱。通过实时 PCR、western blot 分析和免疫组织化学染色，在肾小球、培养的足细胞和人和小鼠的尿液样本中检测 mindin 的表达。
喂食 HC 的小鼠出现足细胞足突融合。HC 组小鼠的 mindin 蛋白表达水平定位于足细胞，其在肾小球中的水平高于 SD 组。在 16 周龄时，HC 组的尿 mindin 水平也明显高于 SD 组，尽管两组的白蛋白/肌酐比值（ACR）没有差异。此外，T2D 患者的水平高于健康个体，并且随着 ACR 的增加逐渐升高。
Mindin 可能与足细胞损伤有关，并且似乎是糖尿病肾病进展的早期生物标志物。
