2014 Fiscal Year Annual Research Report
ミッドカインによる内皮細胞由来の血管作動因子を介した血圧調整のメカニズムの解明
Project/Area Number |
25293195
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Research Institution | Nagoya University |
Principal Investigator |
松尾 清一 名古屋大学, 医学(系)研究科(研究院), 教授 (70190410)
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Co-Investigator(Kenkyū-buntansha) |
湯澤 由紀夫 藤田保健衛生大学, 医学部, 教授 (00191479)
丸山 彰一 名古屋大学, 医学(系)研究科(研究院), 准教授 (10362253)
佐藤 和一 藤田保健衛生大学, 医学部, 准教授 (90508920)
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Keywords | 高血圧症 / ミッドカイン / 血管内皮障害 / 内皮由来血管拡張因子 |
Outline of Annual Research Achievements |
最近、高血圧症には血管拡張作用を持つ液性因子を血管内皮細胞が分泌し、Vascular toneが制御されている事が明らかにされている。血管拡張作用を有するものとして、プロスタグランジンI2、一酸化窒素(NO)、内皮細胞依存性過分極因子(EDHF)でCYP450由来のepoxyeicosatrienoic acids (EETs)が報告されているが、どうのように血管に関与しているかは明らかではない。 本研究では、ミッドカイン(MK)が内皮細胞由来の血管作動性因子を介して血圧を上昇させるメカニズムを解明し、MKを制御する事で高血圧症や血管内皮細胞障害に対する新たな治療法を開発する事を目的とした。これまでに、MK遺伝子欠損マウス(MKKO)と野生型(WT)マウスを用いて片腎摘マウスを作成し、NO合成酵素阻害剤L-NAMEを投与したところWTマウスではMKKOマウスと比べ、高血圧、腎機能障害をより強く呈したことを示した。その際、RAASやエンドセリンでは優位な差を認めなかった。一方で、血管拡張因子であるEETsの代謝産物の14, 15-DHETはMKKOマウスにて優位な上昇を認めていた。その後、EETsカスケード阻害剤をMKKOマウスに投与すると、血圧の上昇を認めた。また、血清ノルアドレナリン濃度の上昇を認めた。上記の結果を基とし、EETs阻害剤の投与により腎微小血管循環の変化を検証した。生体顕微鏡によりperitubular capilaryを観察し、阻害剤により循環流量の40%程度の減少を示した。血管内皮障害を軽減させる事により高血圧や臓器障害を治療するための前臨床試験を動物実験によって行い、血管作動性因子や血管平滑筋細胞との相互作用の検証やメタボローム解析を使用したメカニズムの解明と新規関連因子の同定を今後もさらなる検討が必要であると考えられた。
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Research Progress Status |
26年度が最終年度であるため、記入しない。
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Strategy for Future Research Activity |
26年度が最終年度であるため、記入しない。
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Causes of Carryover |
26年度が最終年度であるため、記入しない。
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Expenditure Plan for Carryover Budget |
26年度が最終年度であるため、記入しない。
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Research Products
(82 results)
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[Journal Article] Midkine Regulates BP through Cytochrome P450-Derived Eicosanoids.2014
Author(s)
Sato Y, Sato W, Maruyama S, Wilcox CS, Falck JR, Masuda T, Kosugi T, Kojima H, Maeda K, Furuhashi K, Ando M, Imai E, Matsuo S, Kadomatsu K.
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Journal Title
J Am Soc Nephrol
Volume: Epub
Pages: Epub
Peer Reviewed
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[Journal Article] Patient age and the prognosis of idiopathic membranous nephropathy.2014
Author(s)
Yamaguchi M, Ando M, Yamamoto R, Akiyama S, Kato S, Katsuno T, Kosugi T, Sato W, Tsuboi N, Yasuda Y, Mizuno M, Ito Y, Matsuo S, Maruyama S.
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Journal Title
PLoS One
Volume: 9(10)
Pages: e110376
DOI
Peer Reviewed
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[Journal Article] Outcomes of primary nephrotic syndrome in elderly Japanese: retrospective analysis of the Japan Renal Biopsy Registry (J-RBR).2014
Author(s)
Yokoyama H, Sugiyama H, Narita I, Saito T, Yamagata K, Nishio S, Fujimoto S, Mori N, Yuzawa Y, Okuda S, Maruyama S, Sato H, Ueda Y, Makino H, Matsuo S.
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Journal Title
Clin Exp Nephrol
Volume: Epub
Pages: Epub
Peer Reviewed
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[Journal Article] Impact of circulating cathepsin K on the coronary calcification and the clinical outcome in chronic kidney disease patients.2014
Author(s)
Izumi Y, Hayashi M, Morimoto R, Cheng XW, Wu H, Ishii H, Yasuda Y, Yoshikawa D, Izawa H, Matsuo S, Oiso Y, Murohara T.
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Journal Title
Heart Vessels
Volume: Epub
Pages: Epub
Peer Reviewed
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[Journal Article] Smoking is a risk factor for the progression of idiopathic membranous nephropathy.2014
Author(s)
Yamaguchi M, Ando M, Yamamoto R, Akiyama S, Kato S, Katsuno T, Kosugi T, Sato W, Tsuboi N, Yasuda Y, Mizuno M, Ito Y, Matsuo S, Maruyama S.
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Journal Title
PLoS One
Volume: 9(6)
Pages: e100835
DOI
Peer Reviewed
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[Journal Article] Immediate therapeutic efficacy of low-density lipoprotein apheresis for drug-resistant nephrotic syndrome: evidence from the short-term results from the POLARIS Study.2014
Author(s)
Muso E, Mune M, Hirano T, Hattori M, Kimura K, Watanabe T, Yokoyama H, Sato H, Uchida S, Wada T, Shoji T, Yuzawa Y, Takemura T, Sugiyama S, Nishizawa Y, Ogahara S, Yorioka N, Sakai S, Ogura Y, Yukawa S, Iino Y, Imai E, Matsuo S, Saito T.
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Journal Title
Clin Exp Nephrol
Volume: Epub
Pages: Epub
Peer Reviewed
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[Journal Article] Impact of albuminuria on the incidence of periprocedural myocardial injury in patients undergoing elective coronary stent implantation.2014
Author(s)
Osugi N, Suzuki S, Ishii H, Yasuda Y, Shibata Y, Tatami Y, Ota T, Kawamura Y, Okumura S, Tanaka A, Inoue Y, Matsuo S, Murohara T.
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Journal Title
Am J Cardiol
Volume: 114(1)
Pages: 42-6
DOI
Peer Reviewed
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[Journal Article] A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy.2014
Author(s)
Kawamura T, Yoshimura M, Miyazaki Y, Okamoto H, Kimura K, Hirano K, Matsushima M, Utsunomiya Y, Ogura M, Yokoo T, Okonogi H, Ishii T, Hamaguchi A, Ueda H, Furusu A, Horikoshi S, Suzuki Y, Shibata T, Yasuda T, Shirai S, Imasawa T, Kanozawa K, Wada A, Matsuo S, Tomino Y(他6名)
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Journal Title
Nephrol Dial Transplant
Volume: 29(8)
Pages: 1546-53
DOI
Peer Reviewed
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[Journal Article] The effect of febuxostat to prevent a further reduction in renal function of patients with hyperuricemia who have never had gout and are complicated by chronic kidney disease stage 3: study protocol for a multicenter randomized controlled study.2014
Author(s)
Hosoya T, Kimura K, Itoh S, Inaba M, Uchida S, Tomino Y, Makino H, Matsuo S, Yamamoto T, Ohno I, Shibagaki Y, Iimuro S, Imai N, Kuwabara M, Hayakawa H.
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Journal Title
Trials
Volume: 16
Pages: 15-26
DOI
Peer Reviewed
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[Journal Article] A multicenter cross-sectional study of circulating soluble urokinase receptor in Japanese patients with glomerular disease.2014
Author(s)
Wada T, Nangaku M, Maruyama S, Imai E, Shoji K, Kato S, Endo T, Muso E, Kamata K, Yokoyama H, Fujimoto K, Obata Y, Nishino T, Kato H, Uchida S, Sasatomi Y, Saito T, Matsuo S.
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Journal Title
Kidney Int
Volume: 85(3)
Pages: 641-8
DOI
Peer Reviewed
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[Journal Article] Comparison of phenotype and outcome in microscopic polyangiitis between Europe and Japan.2014
Author(s)
Furuta S, Chaudhry AN, Hamano Y, Fujimoto S, Nagafuchi H, Makino H, Matsuo S, Ozaki S, Endo T, Muso E, Ito C, Kusano E, Yamagata M, Ikeda K, Kashiwakuma D, Iwamoto I, Westman K, Jayne D.
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Journal Title
J Rheumatol
Volume: 41(2)
Pages: 325-33
DOI
Peer Reviewed
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[Journal Article] Geriatric nutritional risk index accurately predicts cardiovascular mortality in incident hemodialysis patients.2014
Author(s)
Takahashi H, Ito Y, Ishii H, Aoyama T, Kamoi D, Kasuga H, Yasuda K, Maruyama S, Matsuo S, Murohara T, Yuzawa Y.
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Journal Title
J Cardio
Volume: 64(1)
Pages: 32-6
DOI
Peer Reviewed
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[Journal Article] Rat adipose tissue-derived stem cells attenuate peritoneal injuries in rat zymosan-induced peritonitis accompanied by complement activation.2014
Author(s)
Kim H, Mizuno M, Furuhashi K, Katsuno T, Ozaki T, Yasuda K, Tsuboi N, Sato W, Suzuki Y, Matsuo S, Ito Y, Maruyama S.
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Journal Title
Cytotherapy
Volume: 16(3)
Pages: 357-68
DOI
Peer Reviewed
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[Journal Article] Significance of combined cyclosporine-prednisolone therapy and cyclosporine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome: a randomized controlled multicenter trial.2014
Author(s)
Saito T, Iwano M, Matsumoto K, Mitarai T, Yokoyama H, Yorioka N, Nishi S, Yoshimura A, Sato H, Ogahara S, Shuto H, Kataoka Y, Ueda S, Koyama A, Maruyama S, Nangaku M, Imai E, Matsuo S, Tomino
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Journal Title
Clin Exp Nephrol
Volume: 18(5)
Pages: 784-94
DOI
Peer Reviewed
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[Journal Article] Long-term effects of spironolactone in peritoneal dialysis patients.2014
Author(s)
Ito Y, Mizuno M, Suzuki Y, Tamai H, Hiramatsu T, Ohashi H, Ito I, Kasuga H, Horie M, Maruyama S, Yuzawa Y, Matsubara T, Matsuo S
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Journal Title
J Am Soc Nephrol
Volume: 25(5)
Pages: 1094-102
DOI
Peer Reviewed
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[Journal Article] CD147/basigin reflects renal dysfunction in patients with acute kidney injury.2014
Author(s)
Nagaya H, Kosugi T, Maeda-Hori M, Maeda K, Sato Y, Kojima H, Hayashi H, Kato N, Ishimoto T, Sato W, Yuzawa Y, Matsuo S, Kadomatsu K, Maruyama S.
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Journal Title
Clin Exp Nephrol
Volume: 18(5)
Pages: 746-54
DOI
Peer Reviewed
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[Journal Article] Overestimation of the risk of progression to end-stage renal disease in the poor prognosis' group according to the 2002 Japanese histological classification for immunoglobulin A nephropathy.2014
Author(s)
Miyazaki Y, Kawamura T, Joh K, Okonogi H, Koike K, Utsunomiya Y, Ogura M, Matsushima M, Yoshimura M, Horikoshi S, Suzuki Y, Furusu A, Yasuda T, Shirai S, Shibata T, Endoh M, Hattori M, Akioka Y, Katafuti R, Hashiguchi A, Kimura K, Matsuo S, Tomino Y.
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Journal Title
Clin Exp Nephrol
Volume: 18(3)
Pages: 475-80
DOI
Peer Reviewed
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[Presentation] Vascular Endothelial Growth Factor Receptor-3 Can Be a New Target to Improve Ultrafiltration Dysfunction in Methylglyoxal-Induced Peritoneal Injury2014
Author(s)
Takeshi Terabayashi, MD, Yasuhiko Ito, MD, PhD, Masashi Mizuno, MD, PhD, Yasuhiro Suzuki, MD, Hiroshi Kinashi, MD, Fumiko Sakata, Shoichi Maruyama, MD, Yoshifumi Takei, PhD, Seiichi Matsuo, MD.
Organizer
Kidney Week 2014
Place of Presentation
フィラデルフィア (米国)
Year and Date
2014-11-11 – 2014-11-16
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[Presentation] High Ferritin Level and Low Nutrition Status Predicts Higher Risk of Infection-Related Hospitalization in Incident Dialysis Patients: A Japanese Prospective Cohort Study2014
Author(s)
Sawako Kato, MD, PhD, Shoichi Maruyama, MD, Bengt Lindholm, MD, PhD, Yukio Yuzawa, MD, Yoshinari Tsuruta, MD, Seiichi Matsuo, MD.
Organizer
Kidney Week 2014
Place of Presentation
フィラデルフィア (米国)
Year and Date
2014-11-11 – 2014-11-16
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[Presentation] Aortic Calcification Was Accelerated After Radical Nephrectomy: Clinical Impact of GFR Decline for Vascular Calcification2014
Author(s)
Yoshinari Yasuda, MD, PhD, Akitaka Suzuki, MD, Ryohei Hattori, MD, Yasuhito Funahashi, MD, PhD, Shoichi Maruyama, MD, Seiichi Matsuo, MD. CKD
Organizer
Kidney Week 2014
Place of Presentation
フィラデルフィア (米国)
Year and Date
2014-11-11 – 2014-11-16
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[Presentation] The Growth Factor Midkine Reflect the Disease Activity in Lupus Nephritis2014
Author(s)
Tomohiro Masuda, MD, Kayaho Maeda, MD, Waichi Sato, MD, PhD, Tomoki Kosugi, MD, PhD, Yuka Sato, MD, Takuji Ishimoto, MD, PhD, Seiichi Matsuo, MD, Shoichi Maruyama, MD.
Organizer
Kidney Week 2014
Place of Presentation
フィラデルフィア (米国)
Year and Date
2014-11-11 – 2014-11-16
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[Presentation] Home Blood Pressure Telemonitoring System Among Patients with CKD: An Attempt to Achieve Optimal Blood Pressure Control with Real-Time Remote.2014
Author(s)
Yoshinari Yasuda, MD, PhD, Misao Niwa, Kanako Shibata, Mayumi Kamiya, Imai Junko, Sawako Kato, MD, PhD, Shoichi Maruyama, MD, Seiichi Matsuo, MD.
Organizer
Kidney Week 2014
Place of Presentation
フィラデルフィア (米国)
Year and Date
2014-11-11 – 2014-11-16
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[Presentation] Effects of Educational Intervention on Renal Outcome of Early- to Moderate-Stage Chronic Kidney Disease: A Cluster-Randomized Trial2014
Author(s)
Kunihiro Yamagata, MD, PhD, Hirofumi Makino, MD, PhD, Kunitoshi Iseki, MD, Sadayoshi Ito, MD, PhD, Kenjiro Kimura, MD, Eiji Kusano, MD, Kimio Tomita, MD, Ichiei Narita, MD, PhD, Tomoya Nishino, MD, PhD, Yoshihide Fujigaki, DrMed, Tsuyoshi Watanabe, MD, Takashi Wada, MD, PhD, Seiichi Matsuo, MD.
Organizer
Kidney Week 2014
Place of Presentation
フィラデルフィア (米国)
Year and Date
2014-11-11 – 2014-11-16
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[Presentation] Association of Glomerular Macrophage Phenotypes and Urinary Soluble CD163 with Disease Activity in Human Lupus Nephritis2014
Author(s)
Nobuhide Endo, DrMed, Naotake Tsuboi, MD, PhD, Kazuhiro Furuhashi, MD, PhD, Shoichi Maruyama, MD, Seiichi Matsuo, MD.
Organizer
Kidney Week 2014
Place of Presentation
フィラデルフィア (米国)
Year and Date
2014-11-11 – 2014-11-16
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[Presentation] Smoking Is a Risk Factor for the Relapse of Antineutrophil Cytoplasmic Antibody (ANCA-Associated Vasculitis.2014
Author(s)
Makoto Yamaguchi, MD, Sawako Kato, MD, PhD, Takuji Ishimoto, MD, PhD, Tomoki Kosugi, MD, PhD, Waichi Sato, MD, PhD, Naotake Tsuboi, MD, PhD, Masashi Mizuno, MD, PhD, Yasuhiko Ito, MD, PhD, Seiichi Matsuo, MD, Shoichi Maruyama, MD.
Organizer
Kidney Week 2014
Place of Presentation
フィラデルフィア (米国)
Year and Date
2014-11-11 – 2014-11-16
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[Presentation] Plasma CD147/Basigin as a Promising Biomarker of the Kidney Diseases2014
Author(s)
Kayaho Maeda, MD, Tomoki Kosugi, MD, PhD, Hiroshi Kojima, MD, Tomohiro Masuda, MD, Noritoshi Kato, MD, PhD, Waichi Sato, MD, PhD, Seiichi Matsuo, MD,
Organizer
Kidney Week 2014
Place of Presentation
フィラデルフィア (米国)
Year and Date
2014-11-11 – 2014-11-16
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[Presentation] Low Awareness and Comprehension of Chronic Kidney Disease Among Japanese Health-Check Subjects2014
Author(s)
Yoshinari Yasuda, MD, PhD, Mayumi Kamiya, Yohei Maeshima, MD, PhD, Tadao Akizawa, MD, Seiichi Matsuo, MD, Shoichi Maruyama, MD.
Organizer
Kidney Week 2014
Place of Presentation
フィラデルフィア (米国)
Year and Date
2014-11-11 – 2014-11-16
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[Presentation] 膜性腎症とPLA2R2014
Author(s)
丸山 彰一、秋山 真一、松尾 清一
Organizer
第57回日本腎臓学会学術総会
Place of Presentation
パシフィコ横浜(神奈川県横浜市)
Year and Date
2014-07-04 – 2014-07-06
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[Presentation] Spironolactone improving intrarenal renin-angiotensin system activation in type 2diabetic nephropathy patients with overt albuminuria.2014
Author(s)
Sawako Kato, Shoichi Maruyama, Hirofumi Makino, Jun Wada, Takashi Uzu, Hisazumi Araki, Daisuke Koya,Keizo Kanasaki, Akira Nishiyama, Hiroyuki Kobori,Enyu Imai,Masahiko Ando, Yutaka Oiso, Seiichi Matsuo
Organizer
The 14th Asian Pacific Congress of Nephrology
Place of Presentation
東京(港区,品川プリンスホテル)
Year and Date
2014-05-14 – 2014-05-17
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