Molecular biological analysis of the mechanism of acute renal failure

急性肾衰竭机制的分子生物学分析

• 批准号: 07457242
• 负责人: TOMITA Kimio
• 金额: $ 4.03万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457242/
• 关键词: acute renal failure; gene; glomerulus; tubules; endothelin; receptor

We investigated the expression and regulation of endothelin-1 protein and mRNA,endothelin converting enzyme protein and mRNA,A type endothelin receptor mRNA,B type endothelin receptor mRNA in ischemic and cyclosporine-induced acute renal failure. Endothelin-1 mRNA started to increase from 30 minutes to several hours after ischemic insult or cyclosporine administration. A type endothelin receptor mRNA decreased in both types of acute renal failure. B type endothelin receptor mRNA increased in ischemic acute renal failure. However, it decreased in cyclosporine-induced acute renal failure. Endothelin converting enzyme protein and mRNA decreased in cyclosporine-induced acute renal failure. To elucidate the mechanism of inhibition of endothelin converting enzyme protein and mRNA,regulation of endothelin converting enzyme was investigated in cultured endothelial cells. Endothelin-1 has an inhibitory effect on endothelin converting enzyme protein and mRNA through B type endothelin receptor. These data suggests that impairments of renal function may be protected by the decrease in A type endothelin receptor and increase in B type endothelin receptor in ischemic acute renal failure. As for cyclosporine-induced acute renal failure, impairments of renal function may be protected by the decrease in A type endothelin receptor and decrease in endothelin converting enzyme through B type endothelin receptor.

本研究探讨了内皮素-1（ET-1）、内皮素转换酶（ET-1）、A型内皮素受体（ET-A）、B型内皮素受体（ET-B）在缺血性和环孢素A（CsA）诱导的急性肾功能衰竭中的表达及调控。内皮素-1mRNA在缺血损伤或环孢霉素给药后30分钟至数小时开始增加。A型内皮素受体mRNA在两型急性肾功能衰竭中均降低。缺血性急性肾功能衰竭时B型内皮素受体mRNA表达增加。然而，在环孢素引起的急性肾功能衰竭中，它降低。环孢素A致急性肾功能衰竭时内皮素转换酶蛋白和mRNA表达降低。为了阐明抑制内皮素转换酶蛋白和mRNA的机制，在培养的内皮细胞中研究内皮素转换酶的调节。内皮素-1通过B型内皮素受体对内皮素转换酶蛋白和mRNA产生抑制作用。提示缺血性急性肾功能衰竭时，A型内皮素受体的减少和B型内皮素受体的增加可能对肾功能损害起保护作用。对于环孢菌素引起的急性肾衰竭，肾功能损害可能通过A型内皮素受体减少和通过B型内皮素受体减少内皮素转换酶来保护。

项目成果

Y.Kitamoto,H.: "Vascular endothelial growth factor (VEGF) is an essential molecule for mouse kidney development : glomerulogenesis and nephrogenesis." J.Clin.Invest.(in press).

Y.Kitamoto,H.：“血管内皮生长因子 (VEGF) 是小鼠肾脏发育的重要分子：肾小球发生和肾发生。”

H.Nonoguchi,: "Role of urinary arginine vasopressin in the sodium excretion in patients with chronic renal failure." Am.J.Med Sci. 312. 195-201 (1996)

H.Nonoguchi，：“尿精氨酸加压素在慢性肾功能衰竭患者钠排泄中的作用。”

Y.Terada,et al: "Presence and regulation of Raf-1-K (kinase),MAPK-K,MAP-K,and S6-K in rat nephron segments." J.Am.Soc.Nephrol.6. 1565-1577 (1995)

Y.Terada 等人：“大鼠肾单位段中 Raf-1-K（激酶）、MAPK-K、MAP-K 和 S6-K 的存在和调节。”

T.Yamada: "AVP inhibits EGF-stimulated MAP kinase cascade in Madin-Darby canine kidney cells." J.Am.Soc.Nephrol. 6. 1565-1577 (1995)

T.Yamada：“AVP 抑制 Madin-Darby 犬肾细胞中 EGF 刺激的 MAP 激酶级联。”

T.Yamada,et al: "AVP inhibits EGF-stimulated MAP kinase cascade in Madin-Darby canine kidney cells." Kidney Int.48. 745-752 (1995)

T.Yamada 等人：“AVP 抑制 Madin-Darby 犬肾细胞中 EGF 刺激的 MAP 激酶级联。”