Division of Clinical Pharmacology, Department of Pharmacology, School of Medicine, Jichi Medical University, Shimotsuke 329-0498, Japan.
Toxicology. 2011 Nov 28;290(1):82-8. doi: 10.1016/j.tox.2011.08.019. Epub 2011 Sep 3.
Because traditional markers for detecting renal injury are generally insensitive and nonspecific, we tried to identify some useful biomarkers. Microarray analyses and quantitative real-time PCR using human renal tubular cells showed that the mRNA expression of VNN-1 which encodes vanin-1, increased after the exposure of these cells to organic solvents (allyl alcohol, ethylene glycol, formaldehyde, chloroform, and phenol) for 24h. The mRNA levels of other inflammation-related molecules such as monocyte chemoattractant protein 1 (MCP-1) and kidney injury molecule-1 (KIM-1) also increased after the exposure to organic solvents, although their elevations were slower than that of vanin-1. In rats treated with ethylene glycol for 3 weeks, tubular injury was detected by histological examination, but not by traditional biomarkers including serum creatinine and urinary N-acetyl-β-glucosaminidase. The mRNA levels of vanin-1 and Kim-1, but not MCP-1, significantly elevated in the renal cortices of ethylene glycol-exposed rats. On immunofluorescence analyses, vanin-1 signal was detected specifically in the renal tubules with a remarkable expression in the ethylene glycol-treated rats. As a result, compared with control group, higher urinary and serum concentrations of vanin-1 were observed in the ethylene glycol-treated group. These results suggest that vanin-1 is a useful and rapid biomarker for renal tubular injury induced by organic solvents.
由于传统的用于检测肾损伤的标志物通常不敏感且特异性不强，我们试图寻找一些有用的生物标志物。使用人类肾小管细胞的微阵列分析和实时定量 PCR 显示，编码 vanin-1 的 VNN-1 的 mRNA 表达在这些细胞暴露于有机溶剂（烯丙醇、乙二醇、甲醛、氯仿和苯酚）24 小时后增加。其他炎症相关分子（如单核细胞趋化蛋白 1 (MCP-1) 和肾损伤分子 1 (KIM-1)）的 mRNA 水平在接触有机溶剂后也增加，尽管它们的升高速度比 vanin-1 慢。在接受乙二醇治疗 3 周的大鼠中，通过组织学检查检测到肾小管损伤，但传统的标志物（包括血清肌酐和尿 N-乙酰-β-氨基葡萄糖苷酶）没有检测到。Vanin-1 和 Kim-1 的 mRNA 水平，而不是 MCP-1，在乙二醇暴露的大鼠的肾皮质中显著升高。在免疫荧光分析中，vanin-1 信号在肾小管中特异性检测到，在乙二醇处理的大鼠中表达明显。因此，与对照组相比，在乙二醇处理组中观察到更高的尿中和血清中的 vanin-1 浓度。这些结果表明，vanin-1 是有机溶剂诱导的肾小管损伤的一种有用且快速的生物标志物。
