Analysis of the function of prostasin in the transgenic mice.

转基因小鼠前列腺素的功能分析。

• 批准号: 14370321
• 负责人: TOMITA Kimio
• 金额: $ 8.83万
• 依托单位: Kumamoto University Graduate School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370321/
• 关键词: Na channel; hypertension; kidney; serine protease; collecting tubule; 上皮性Naチャネル; プロスタシン; 腎臓; Na代謝

Sodium regulation in the kidney is one of the most important factors for the regulation of blood pressure. Epithelial sodium channel is key protein in the regulation of Na balance. We reported that a new serine protease prostasin can activate epithelial sodium channel in cultured cells. Prostasin was stimulated by aldosterone in vitro and in vivo experiments. In human, urinary prostasin excretion was elevated in primary aldosteronism, suggesting that prostasin may have significant roles in the regulation of blood pressure. Therefore, we have investigated to elucidate the roles of prostasin in the regulation of blood pressure by use of transgenic mice harboring prostasin gene. At first, we have isolated human prostasin cDNA. We have already isolated 3 BAC clones which contained human prostasin gene. This projects is now underway. We must continue further experiments.

肾脏中的钠调节是调节血压的最重要因素之一。上皮细胞钠通道是调节钠平衡的关键蛋白。我们报道了一种新的丝氨酸蛋白酶prostasin能激活培养细胞的上皮钠通道。前列腺素在体外和体内实验中被醛固酮刺激。原发性醛固酮增多症患者尿前列腺素排泄量增加，提示前列腺素可能在血压调节中起重要作用。因此，我们利用转前列腺素基因小鼠，研究前列腺素在血压调节中的作用。首先，我们分离了人前列腺素cDNA。我们已经分离到3个含有人前列腺素基因的BAC克隆。这些项目目前正在进行中。我们必须继续进行进一步的实验。

项目成果

"Two male siblings with hereditary renal hypouricemia and exercise-induced ARF"Am.J.Kid.Dis.. 42. 1287-1292 (2003)

“两个患有遗传性肾性低尿酸血症和运动引起的 ARF 的男性兄弟姐妹”Am.J.Kid.Dis.. 42. 1287-1292 (2003)

Kikuchi Y, N.Nonoguchi, K.Machida, S.Wakamatsu, H.Koga, K.Tomita: "Regulation of the apoptosis-related genes, Bax and Bcl-2, in the early stage of diabetes mellitus."Nephrology. 7. 294-302 (2002)

Kikuchi Y、N.Nonoguchi、K.Machida、S.Wakamatsu、H.Koga、K.Tomita：“糖尿病早期阶段细胞凋亡相关基因 Bax 和 Bcl-2 的调节。”肾脏病学。

Okumura Y, et al.: "Cloning and characterization of a transmembrane-type serine protease from rat kidney, a new sodium channel activator"Biol Chem.. 384. 1483-1495 (2003)

Okumura Y 等人：“来自大鼠肾脏的跨膜型丝氨酸蛋白酶的克隆和表征，一种新的钠通道激活剂”Biol Chem.. 384. 1483-1495 (2003)

Narikiyo T., et al.: "Regulation of prostasin by aldosterone in the kidney."J.Clin.Invest.. 109. 401-408 (2002)

Narikiyo T. 等人：“肾脏中醛固酮对前列腺素的调节。”J.Clin.Invest.. 109. 401-408 (2002)

Kurokawa K, K.Abe, T.Saruta, M.Arakawa, R.Kikkawa, N.Ueda, K.Onoyama, K.Tomita, N.Ogawa: "Antiproteinuric effect of candesartan cilexetil in patients with chronic glomerulonephritis."J.Renin-Angiotensin-Aldosterone System.. 3. 167-175 (2002)

Kurokawa K、K.Abe、T.Saruta、M.Arakawa、R.Kikkawa、N.Ueda、K.Onoyama、K.Tomita、N.Okawa：“坎地沙坦西酯对慢性肾小球肾炎患者的抗蛋白尿作用。”J。