2014 Fiscal Year Annual Research Report
抗体結合型バイオナノカプセルを応用した炎症白血球特異的新規腎障害治療法の開発
Project/Area Number |
25670408
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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) |
坪井 直毅 名古屋大学, 医学部附属病院, 講師 (50566958)
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Keywords | マクロファージ / バイオナノカプセル / 腎虚血再灌流障害 / ドラッグデリバリー |
Outline of Annual Research Achievements |
慢性腎炎や糖尿病性腎症など主な慢性腎臓病(CKD)の発症・進展過程に共通する最も重要な機序に炎症があげられるが、従来の全身的免疫抑制療法では効果に限界があり、また重篤な副作用は極めて深刻な治療中断規定因子となっている。今回の研究ではバイオナノカプセル(BNC)を応用したドラッグデリバリーシステム(DDS)により、CKDにおいて腎組織障害の中心的役割を担う好中球・マクロファージ(Mφ)を選択的かつ炎症部位特異的に機能抑制することで、抗炎症・免疫抑制効果と副作用の軽減を両立させた革新的な治療法開発を目指した。 平成25年度はCy3標識したZZ-tag提示型BNCに、CD11b抗体(cloneM1/70)を結合させ細胞分子特異的BNCを作成(BNC-・IgG)した。さらにCy3標識したZZ-tag提示型BNCに、抗CD11b抗体を結合させ、マウスマクロファージ細胞株(RAW264.7)に添加したところ、BNCの局在を共焦点レーザー顕微鏡で確認することができた。次に蛍光標識した抗CD11b抗体接合BNCをマウスに経静脈投与したところIRI作成腎皮髄境界部優位なCy3陽性細胞を認めたが、非虚血腎には所見をみなかった。平成26年度は治療薬剤非封入下でのBNC-αIgG腎毒性と治療効果を検討した。BNC投与群ではコントロール群に比しIRIの疾患強度に差は認められず、薬剤非封入BNC、あるいはBNCに結合したモノクローナル抗体自体は治療効果も、障害悪化作用も有さないことが示唆された。しかしながらGFP発現コンストラクトを封入したBNC-αIgGを作成し、in vitroでRAW264.7細胞での発現確認を行ったが有意なGFP発現をみなかった。今後、遺伝子発現を実現できる条件設定が整った場合には、治療薬剤封入BNC-・IgGのin vitroでの抗炎症・免疫抑制効果判定,治療薬剤封入BNC-・IgGのin vivo治療効果判定,他の腎疾患への応用研究を実現したいと考えている。
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[Journal Article] Midkine Regulates BP through Cytochrome P450-Derived Eicosanoids.2015
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: inpress
Pages: inpress
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).2015
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: inpress
Pages: inpress
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.2015
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] 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 M1, 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] 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] Taming the chronic kidney disease epidemic: a global view of surveillance efforts.2014
Author(s)
Radhakrishnan J, Remuzzi G, Saran R, Williams DE, Rios-Burrows N, Powe N; CDC-CKD Surveillance Team, Brück K, Wanner C, Stel VS; European CKD Burden Consortium, Venuthurupalli SK, Hoy WE, Healy HG, Salisbury A, Fassett RG; CKD.QLD group, O'Donoghue D, Roderick P, Matsuo S, Hishida A, Imai E, Iimuro S.
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Journal Title
Kidney Int
Volume: 86(2)
Pages: 246-50
DOI
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, Yamaji I, Miura N, Matsuo S, Tomino Y.他4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: 15
Pages: 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 Cardiol
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 Y
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Journal Title
Clin Exp Nephrol
Volume: 18(5)
Pages: 784-94
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 Neph
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
品川プリンスホテル(東京都港区)
Year and Date
2014-05-14 – 2014-05-17
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