Toyoda Masao, Suzuki Daisuke, Umezono Tomoya, Uehara Goro, Maruyama Mayumi, Honma Masashi, Sakai Takako, Sakai Hideto
Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Nephrol Dial Transplant. 2004 Feb;19(2):380-5. doi: 10.1093/ndt/gfg545.
Diabetic nephropathy (DN) is associated with functional changes in the filtration barrier, and microalbuminuria is a strong predictor of the development of overt DN. Nephrin is a novel podocyte-specific protein which localizes at the slit diaphragm. This study examines the expression of nephrin mRNA in the kidneys of type 2 diabetics with DN.
Renal tissues were obtained from 13 type 2 diabetics with DN. We also examined samples from five patients with minimal change nephrotic syndrome (MCNS) and five normal kidneys (normals) as control. The severity of DN was classified into two grades based on histopathological findings. DN grade 1 (DN1 = seven patients) presented mild mesangial expansion, and DN grade 2 (DN2 = six patients) moderate mesangial expansion. Nephrin mRNA was quantitated and localized by in situ hybridization.
Cells positive for nephrin mRNA were detected exclusively in glomerular epithelial cells. The percentage of cells positive for nephrin mRNA in DN2 was significantly lower than in MCNS and normal kidneys. Furthermore, there was an inverse correlation between the percentage of cells positive for nephrin mRNA and extent of proteinuria.
The low expression of nephrin mRNA may be closely linked to development and/or progression of proteinuria in human diabetic nephropathy.
糖尿病肾病（DN）与滤过屏障的功能改变有关，微量白蛋白尿是显性DN发生的有力预测指标。Nephrin是一种新的足细胞特异性蛋白，定位于裂孔隔膜。本研究检测了DN 2型糖尿病患者肾脏中nephrin mRNA的表达。
从13例DN 2型糖尿病患者获取肾组织。我们还检测了5例微小病变肾病综合征（MCNS）患者和5例正常肾脏（正常组）的样本作为对照。根据组织病理学结果将DN的严重程度分为两级。DN 1级（DN1 = 7例患者）表现为轻度系膜扩张，DN 2级（DN2 = 6例患者）表现为中度系膜扩张。通过原位杂交对nephrin mRNA进行定量和定位。
仅在肾小球上皮细胞中检测到nephrin mRNA阳性细胞。DN2中nephrin mRNA阳性细胞的百分比显著低于MCNS和正常肾脏。此外，nephrin mRNA阳性细胞的百分比与蛋白尿程度呈负相关。
nephrin mRNA的低表达可能与人类糖尿病肾病蛋白尿的发生和/或进展密切相关。
