2000 Fiscal Year Annual Research Report

腎機能障害進展抑制におけるNa利尿ペプチド系の意義とその分子機構

Research Project

Project/Area Number	11671066
Research Institution	KYOTO UNIVERSITY
Principal Investigator	菅原照京都大学, 医学研究科, 助手 (00312223)
Keywords	Na利尿ペプチド / 血圧 / 腎機能障害 / CTGF / トランスジェニックマウス / 抗糸球体基底膜腎炎 / 腎保護作用 / レニン・アンジオテンシン系
Research Abstract	1.腎疾患モデルにおけるNa利尿ペプチド系の病態生理学的意義腎障害モデル動物(抗糸球体基底膜腎炎、STZ糖尿病性腎症および尿細管結紮水腎症モデル)をラット・マウスで確立し、Na利尿ペプチドならびにその受容体の局在をNothern blot法および既に開発に成功した抗ANP、抗BNP、抗CNPモノクローナル抗体を用いた免疫組織化学的方法により検討し、腎障害の進行の指標になる可能性が示された。 2.Na利尿ペプチド系とレニン・アンジオテンシン系の相互作用に関する検討 Na利尿ペプチド系はレニン・アンジオテンシン系に拮抗的に働くが、その細胞内機序について検討する目的で培養メサンギウム細胞などを用いて細胞内情報伝達系、TGF-β、CTGFや細胞外基質の発現アポトーシス誘導についての相互作用を検討した。ラットCTGFをクローニングしその構造を決定し、さらにCTGFに特異的な抗体作製に成功し、ヒト血中尿中CTGF濃度測定システムを確立した。 3.BNP過剰発現マウスの腎保護作用とその分子機序既に、BNP過剰発現トランスジェニックマウスを用いて腎内レニン・アンジオテンシン系を活性化する5/6腎摘モデルを作製し、対照マウスでは著明な糸球体肥大と腎障害を示すのに対し、BNP過剰発現マウスではその変化は極めて軽度であり、過剰なBNPが腎保護的に働く結果を得、これを報告した。このマウスを用いて尿細管結紮水腎症モデルを作製し腎間質障害も対照マウスに比べて軽度でありBNPが糸球体とともに間質障害に関しても腎保護的に働くことを見出した。さらにこのトランスジェニックマウスに抗糸球体基底膜腎炎、STZ糖尿病性腎症などのモデルを作製しその腎保護効果を示した。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Masato Kasahara: "Ameliorated glomerular injury in mice overexpressing brain natriuretic peptide with renal ablation."Journal of American Society of Nephrology. 11(9). 1691-1701 (2000)
[Publications] Tetsuya Nagae: "Rat receptor-activity-modifying proteins (RAMPs) for adrenomedullin/CGRF receptor : Cloning and upregulation in obstructive nephropathy."Biochemical and Biophysical Research Communications. 270(1). 89-93 (2000)
[Publications] Kensei Yahata: "Molecular cloning and expression of a novel klotho-related protein."Journal of Molecular Medicine. 78(7). 389-394 (2000)
[Publications] Kiyoshi Mori: "Disruption of klotho gene causes an abnormal energy homeostasis in mice."Biochemical and Biophysical Research Communications. 278(3). 665-670 (2000)
[Publications] Kiyoshi Mori: "Kidney produces a novel acylated peptide, ghrelin."FEBS Letters. 486(3). 213-216 (2000)
[Publications] Saori Joyama: "C4 and C4bp deposition along the glomerular capillary walls in a patient with preeclampsia."American Journal of Kidney Disease. 37(1). 1-5 (2000)
[Publications] Masato Kotani: "Multiple signal transduction pathways through two prostaglandin E receptor EP3 subtype isoforms expressend in human uterus."Journal of Clinical Endocrinology and Metabolism. 85(11). 4315-4322 (2001)
[Publications] Atsuo Tanaka: "Chinese herb nephropathy in Japan presents adult-onset Fanconi syndrome : Could different components of aristolochic acids cause a different type of Chinese herb nephropathy?"Clinical Nephrology. 53(4). 301-306 (2001)
[Publications] Takayoshi Suganami: "Altered growth response to prostaglandin E2 and its receptor signaling in mesangial cells from stroke-prone spontaneously hypertensive rats."Journal of Hypertension. (発表予定). (2001)
[Publications] Masayo Nakagawa: "Monoclonal antibody against brain natriuretic peptide (BNP) and characterization of BNP-transgenic mice."Journal of Hypertension. (発表予定). (2001)
[Publications] Hideki Yokoi: "Intraglomerular Metastasis From Pancreatic Cancer."American Journal of Kidney Disease. (発表予定). (2001)

2000 Fiscal Year Annual Research Report

腎機能障害進展抑制におけるNa利尿ペプチド系の意義とその分子機構

Principal Investigator

菅原 照 京都大学, 医学研究科, 助手 (00312223)

Research Products

[Publications] Masato Kasahara: "Ameliorated glomerular injury in mice overexpressing brain natriuretic peptide with renal ablation."Journal of American Society of Nephrology. 11(9). 1691-1701 (2000)

[Publications] Tetsuya Nagae: "Rat receptor-activity-modifying proteins (RAMPs) for adrenomedullin/CGRF receptor : Cloning and upregulation in obstructive nephropathy."Biochemical and Biophysical Research Communications. 270(1). 89-93 (2000)

[Publications] Kensei Yahata: "Molecular cloning and expression of a novel klotho-related protein."Journal of Molecular Medicine. 78(7). 389-394 (2000)

[Publications] Kiyoshi Mori: "Disruption of klotho gene causes an abnormal energy homeostasis in mice."Biochemical and Biophysical Research Communications. 278(3). 665-670 (2000)

[Publications] Kiyoshi Mori: "Kidney produces a novel acylated peptide, ghrelin."FEBS Letters. 486(3). 213-216 (2000)

[Publications] Saori Joyama: "C4 and C4bp deposition along the glomerular capillary walls in a patient with preeclampsia."American Journal of Kidney Disease. 37(1). 1-5 (2000)

[Publications] Masato Kotani: "Multiple signal transduction pathways through two prostaglandin E receptor EP3 subtype isoforms expressend in human uterus."Journal of Clinical Endocrinology and Metabolism. 85(11). 4315-4322 (2001)

[Publications] Atsuo Tanaka: "Chinese herb nephropathy in Japan presents adult-onset Fanconi syndrome : Could different components of aristolochic acids cause a different type of Chinese herb nephropathy?"Clinical Nephrology. 53(4). 301-306 (2001)

[Publications] Takayoshi Suganami: "Altered growth response to prostaglandin E2 and its receptor signaling in mesangial cells from stroke-prone spontaneously hypertensive rats."Journal of Hypertension. (発表予定). (2001)

[Publications] Masayo Nakagawa: "Monoclonal antibody against brain natriuretic peptide (BNP) and characterization of BNP-transgenic mice."Journal of Hypertension. (発表予定). (2001)

[Publications] Hideki Yokoi: "Intraglomerular Metastasis From Pancreatic Cancer."American Journal of Kidney Disease. (発表予定). (2001)

菅原照京都大学, 医学研究科, 助手 (00312223)