Characterization of a novel aspartic proteinase and development of its inhibitor

新型天冬氨酸蛋白酶的表征及其抑制剂的开发

• 批准号: 12557085
• 负责人: IMAI Enyu
• 金额: $ 8.32万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557085/
• 关键词: napsin; collagen Type IV; angiotensin I; renin; 遺伝子発現情報; アンギオテンシン; 新規プロテアーゼ; ゲノム創薬; 発現遺伝子情報; アンギオテンシンII; ノックアウトマウス; 遺伝子情報データベース; 近位尿細管; 腎臓

We cloned a renin-like aspartic proteinase GS4001, which is identified mouse napsin, from mouse proximal tubule.The mouse napsin cleaved angiotensinogen and generated angiotensin I, while the human counterpart napsin did not cleave the angiotensinogen.The mouse napsin has a character of matrix metalloproteinase, and cleaved type IV collagen but not type I collagen.Napsin expression was declined in IgA nephripathy, minimal change nephritic syndrome, crescentic glomerulonephritis. The napsin expression was decreased in mouse BSA-overload model and unilateral ureteral obstruction model.We attempted to generate a new drug, which activates napsin activity to resolve the interstitial fibrosis.

我们从小鼠近曲小管中克隆了一种肾素样天冬氨酸蛋白酶GS4001，经鉴定为小鼠napsin。小鼠napsin裂解血管紧张素原并生成血管紧张素I，而人对应的napsin则不裂解血管紧张素原。小鼠napsin具有基质金属蛋白酶的特性，并且裂解IV型胶原蛋白，但不裂解I型胶原蛋白 胶原蛋白.Napsin在IgA肾病、微小病变肾病综合征、新月体肾小球肾炎中表达下降。在小鼠BSA超载模型和单侧输尿管梗阻模型中，napsin表达降低。我们试图开发一种新药，激活napsin活性以解决间质纤维化。

项目成果

Nakajima H, Takenaka M, Kaimori JY, Nagasawa Y, Kosugi A, Kawamoto S, Imai E, Hori M, Okubo K: "Gene expression profile of renal proximal tubul by proteinuria"Kidney International. 61. 1577-1587 (2002)

Nakajima H、Takenaka M、Kaimori JY、Nagasawa Y、Kosugi A、Kawamoto S、Imai E、Hori M、Okubo K：“蛋白尿对肾近端小管的基因表达谱”肾脏国际。

Nagasawa.Y, Takenaka M, Matsuoka Y, Imai E, Hori M: "Quantitation of mRNA expression in glomeruli using lasermanipulated Microdissection and laser pressure catapulting"Kidney International. 57. 717-723 (2000)

Nagasawa.Y、Takenaka M、Matsuoka Y、Imai E、Hori M：“使用激光显微切割和激光压力弹射对肾小球中 mRNA 表达进行定量”肾脏国际。

Kaimori JY, Takenaka M, Nagasawa Y, Nakajima H, Izumi M, Akagi Y, Imai E, Hori M: "Quantitative analyses of osteopontin mRNA expression in human proximal tubules isolated from renal biopsy tissue sections of minimal change nephrotic syndrome and IgA glome

Kaimori JY、Takenaka M、Nagasawa Y、Nakajima H、Izumi M、Akagi Y、Imai E、Hori M：“从微小病变肾病综合征和 IgA 肾病肾活检组织切片中分离出的人近端小管中骨桥蛋白 mRNA 表达的定量分析

Enyu Imai,Masara Takenaka: "Function genomics in nephrology"Nephrology Dialysis Transplantation. vol15,no2. 139-141 (2000)

Enyu Imai，Masara Takenaka：“肾病学中的功能基因组学”肾病学透析移植。

Nakamura H, Isaka Y, Tsujie M, Rupprecht HD, Akagi Y, Ueda N, Imai E, Hori M: "Introduction of DNA enzyme for Egr-1 into tubulointersutitial fibroblasts by electroporation reduced interstitial α-smooth muscle actin expression and fibrosis in unilateral ob

Nakamura H、Isaka Y、Tsujie M、Rupprecht HD、Akagi Y、Ueda N、Imai E、Hori M：“通过电穿孔将 Egr-1 的 DNA 酶引入肾小管间质成纤维细胞，减少单侧间质 α-平滑肌肌动蛋白表达和纤维化观察