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Prevention of glomerulosed erosis and tubul ointerstitial fibrosis : the effect of antisense ologonucleotide of type I procollagen C-proteinase enhancer protein

预防肾小球性糜烂和肾小管间质纤维化：I型前胶原C-蛋白酶增强蛋白反义寡核苷酸的作用

基本信息

批准号：
09557089
负责人：
TANIGUCHI Shigeo
金额：
$ 7.62万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

It is well known that, whatever the underlying original disease, progressive renal injury is characterized by glomeruloscl erosisand tubulointerstitial fibrosis, which are the common pathological features of chronic renal failure. We have planned the present study to investigate the mechanism of fibrosis in the kidney.First we examined the expression of type I procollagen C-proteinase enhnacer protein, PCPE, which was recently cloned by one of the investigators, Ogata I.By the same author PCPE has been to shown to play an important role in liver fibsosis. We have examined its expression in the kidney by Western blot analysis using cultured rat mesangial cells, normal rat kidney, and 5/6 nephrectomized rat kidney, and we could not detect its expression in the kidney. We also examined the expression of its mRNA by Northern blot analysis, and we could not detect it, neither. So we have concluded that PCPE plays minor role in the pathogenesis of renal fibrosis.We also examined the role of leukotrine B4(LTB4)in the progression of renal diseases. We made hyperlipidemia-induced renal injury in rats, and treated these rats with LTB4 antagonist. This treatment markedly ameliorated kidney injury in these animals. Then we examined the distribution of leukotriene A4 hydrolase mRNA expression in rat nephronsegments, and found that it is present both in glomeruli and tubular segments. These result suggest the important role of LTB4 synthesized in the kidney in the pathogenesis of progressive renal injuries.

众所周知，无论原发病是什么，进行性肾损伤均以肾小球硬化和肾小管间质纤维化为特征，这是慢性肾功能衰竭的共同病理特征。我们计划本研究调查肾脏纤维化的机制。首先，我们检查了 I 型前胶原 C 蛋白酶增强蛋白 PCPE 的表达，该蛋白最近由研究人员之一 Ogata I 克隆。同一作者 PCPE 已被证明在肝纤维化中发挥重要作用。我们使用培养的大鼠系膜细胞、正常大鼠肾脏和5/6肾切除的大鼠肾脏通过Western blot分析检测了其在肾脏中的表达，但我们无法检测到其在肾脏中的表达。我们还通过Northern印迹分析检查了其mRNA的表达，但我们也无法检测到它。因此我们得出结论PCPE在肾纤维化的发病机制中起次要作用。我们还检测了白三碱B4(LTB4)在肾脏疾病进展中的作用。我们制作了高脂血症诱导的大鼠肾损伤模型，并用LTB4拮抗剂治疗这些大鼠。这种治疗显着改善了这些动物的肾损伤。然后我们检测了大鼠肾段中白三烯A4水解酶mRNA表达的分布，发现它同时存在于肾小球和肾小管段中。这些结果表明，肾脏中合成的LTB4在进行性肾损伤的发病机制中发挥着重要作用。