Department of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Am J Nephrol. 2011;34(3):268-80. doi: 10.1159/000330187. Epub 2011 Aug 4.
BACKGROUND/AIMS: Studies have shown that kidney injury molecule-1 (KIM-1) is upregulated in damaged renal proximal tubules. In this study, we examined KIM-1 expression in glomerular epithelial cells in diabetic glomerulopathy.
Renal histology, immunostaining and Western blot for protein level, and real-time PCR for mRNA expression of KIM-1 and podocyte markers were evaluated in untreated or losartan-treated Zucker lean (Fa/+) and Zucker diabetic fatty (Fa/Fa) rats.
The diabetic rats showed an increased glomerular expression of KIM-1. KIM-1 staining was localized primarily in the hyperplastic parietal epithelium of Bowman's capsule in the early stages of diabetes with subsequent increase in KIM-1-positive cells in the glomerular tuft in the more advanced stages. The increase in glomerular KIM-1 was associated with a decrease in podocytes in Fa/Fa rats. Antiproteinuric treatment with losartan attenuated podocytopenia and decreased renal expression of KIM-1 in treated diabetic rats. In an in vitro study, albumin overload increased KIM-1 protein in the primary cultures of rat glomerular epithelial cells.
These results show that glomerular KIM-1 expression was increased, in proportion to the extent of proteinuria and podocytopenia in the diabetic animals, supporting that KIM-1 could be used as a potential biomarker for glomerular injury in proteinuric kidney disease.
背景/目的：研究表明，肾损伤分子-1（KIM-1）在受损的肾近端小管中上调。在本研究中，我们研究了糖尿病肾小球病变中肾小球上皮细胞中 KIM-1 的表达。
在未治疗或氯沙坦治疗的 Zucker 瘦（Fa/ +）和 Zucker 糖尿病肥胖（Fa/Fa）大鼠中评估肾组织学、免疫染色和蛋白质水平的 Western blot 以及 KIM-1 和足细胞标志物的实时 PCR 表达。
糖尿病大鼠的肾小球 KIM-1 表达增加。KIM-1 染色主要定位于糖尿病早期 Bowman 囊的增生壁细胞，随后在更晚期的肾小球丛中 KIM-1 阳性细胞增加。肾小球 KIM-1 的增加与 Fa/Fa 大鼠足细胞减少有关。用氯沙坦进行抗蛋白尿治疗可减轻糖尿病大鼠的足细胞减少并降低肾脏 KIM-1 的表达。在一项体外研究中，白蛋白超负荷增加了大鼠肾小球上皮细胞原代培养物中的 KIM-1 蛋白。
这些结果表明，肾小球 KIM-1 的表达随着糖尿病动物蛋白尿和足细胞减少的程度而增加，支持 KIM-1 可作为蛋白尿性肾病肾小球损伤的潜在生物标志物。
