Treatment strategy based on the pathophysiology of renal-multi-organ axis induced by pathogenic albumin
Project/Area Number |
16H05114
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Medical pharmacy
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Research Institution | Kumamoto University |
Principal Investigator |
Watanabe Hiroshi 熊本大学, 大学院生命科学研究部(薬), 准教授 (70398220)
|
Co-Investigator(Kenkyū-buntansha) |
小田切 優樹 崇城大学, 薬学部, 特任教授 (80120145)
丸山 徹 熊本大学, 薬学部, 教授 (90423657)
|
Project Period (FY) |
2016-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
|
Keywords | アルブミン / 尿毒症物質 / 酸化ストレス / 筋萎縮 / 尿酸 / CYP3A / 脂肪酸代謝 / 腎病態 / 脂肪酸 / 酸化アルブミン / Elovl6 / 腎疾患 / バイカーカー / 尿毒素 / バイオマーカー / 二次性副甲状腺機能亢進症 / 副甲状腺ホルモン / ABCG2 / 薬学 / 腎ー多臓器連関 / 骨格筋 / 腎-多臓器連関 |
Outline of Final Research Achievements |
We focused on the diversity of albumin molecules as a disease-progressing factor of the chronic kidney disease. We investigated 1) the molecular mechanism of skeletal muscle atrophy induced by uremic substances and 2) its therapeutic strategy, 3) the molecular mechanism of secondary hyperparathyroidism (SHPT)-induced hyperuricemia, and 4) the inhibition of CYP3A expression in SHPT, and 5) the molecular mechanism of renal tubular injury associated with renal fatty acid fluctuations, then found that indoxyl sulfate, parathyroid hormone and oxidized albumin were identified as negative humoral factors in chronic kidney disease. We also proposed a therapeutic target based on their molecular mechanism.
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Academic Significance and Societal Importance of the Research Achievements |
慢性腎臓病(CKD)の場合、死亡や要介護状態の原因となる心血管疾患(CVD)や筋力低下(サルコペニア)・骨萎縮を合併しやすいが、既存の治療方法ではその進行を抑制できず、新たな治療戦略の構築が希求されている。本申請課題は、悪玉となる液性因子の探索と、それを基軸とした新規CKD個別化診断・治療戦略の道を拓く循環型のトランスレーション研究である。本研究成果はCKDを基軸とした多臓器連関に対する早期診断・治療に繋がるため、臨床的、社会的意義と波及効果は非常に高く、医療経済的観点からも緊急性は高いと思われる。
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Report
(5 results)
Research Products
(59 results)
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[Journal Article] α1-acid glycoprotein attenuates adriamycin-induced nephropathy via CD163 expressing macrophages induction2020
Author(s)
Fujimura R, Watanabe H, Nishida K, Fujiwara Y, Koga T, Bi J, Imafuku T, Kobayashi K, Komori H, Miyahisa M, Maeda H, Tanaka M, Matsushita K, Wada T, Fukagawa M, Maruyama .
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Journal Title
Kidney360
Volume: in press
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effect of Serum Parathyroid Hormone on Tacrolimus Therapy in Kidney Transplant Patients: A Possible Biomarker for a Tacrolimus Dosage Schedule2019
Author(s)
Hirata K, Watanabe H, Toyoda M, Sugimoto R, Ikegami K, Imafuku T, Matsuzaka K, Ichimizu S, Maeda H, Uekihara S, Jingami S, Maruyama T.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 42
Issue: 5
Pages: 786-791
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2019-05-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cell-penetrating mechanism of intracellular targeting albumin: Contribution of macropinocytosis induction and endosomal escape.2019
Author(s)
Ichimizu S, Watanabe H, Maeda H, Hamasaki K, Ikegami K, Chuang VTG, Kinoshita R, Nishida K, Shimizu T, Ishima Y, Ishida T, Seki T, Katsuki H, Futaki S, Otagiri M, Maruyama T
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Journal Title
J Control Release.
Volume: S0168-3659
Pages: 30174-30177
DOI
Related Report
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[Journal Article] Effect of serum parathyroid hormone on tacrolimus therapy in kidney transplant patients:A possible biomarker for a tacrolimus dosage schedule2019
Author(s)
Hirata K, Watanabe H, Toyoda M, Sugimoto R, Ikegami K, Imafuku T, Matsuzaka K, Ichimizu S, Maeda H, Uekihara S, Jingami S and Maruyama T
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Journal Title
Biol Pharm Bull
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] A downstream molecule of 1,25-dihydroxyvitamin D3, alpha-1-acid glycoprotein, protects against mouse model of renal fibrosis2018
Author(s)
Bi J, Watanabe H, Fujimura R, Nishida K, Nakamura R, Oshiro S, Imafuku T, Komori H, Miyahisa M, Tanaka M, Matsushita K, Maruyama T
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Journal Title
Sci Rep
Volume: 26
Issue: 1
Pages: 17329-17329
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Potential therapeutic interventions for chronic kidney disease-associated sarcopenia via indoxyl sulfate-induced mitochondrial dysfunction2017
Author(s)
Enoki Y, Watanabe H, Arake R, Fujimura R, Ishiodori K, Imafuku K, Nishida K, Sugimoto R, Nagao S, Miyamura S, Ishima Y, Tanaka M, Matsushita K, Komaba H, Fukagawa M, Otagiri M, Maruyama T
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Journal Title
J Cachexia Sarcopenia Muscle
Volume: 8
Issue: 5
Pages: 735-747
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] The down-regulation of ABCG2, a urate exporter, by parathyroid hormone enhances urate accumulation in secondary hyperparathyroidism2017
Author(s)
Sugimoto R, Watanabe H, Ikegami K, Enoki Y, Imafuku T, Sakaguchi Y, Murata M, Nishida K, Miyamura M, Ishima Y, Tanaka M, Matsushita K, Komaba H, Fukagawa M, Otagiri M, Toru Maruyama
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Journal Title
Kidney Int
Volume: 91
Issue: 3
Pages: 658-670
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Human serum albumin hydropersulfide is a potent reactive oxygen species scavenger in oxidative stress conditions such as chronic kidney disease2016
Author(s)
Shibata A, Ishima Y, Ikeda M, Sato H, Imafuku T, Chuang VT, Ouchi Y, Abe T, Watanabe H, Ishida T, Otagiri M, Maruyama T
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Journal Title
Biochem Biophys Res Commun
Volume: 479
Issue: 3
Pages: 578-583
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Indoxyl sulfate potentiates skeletal muscle atrophy by inducing the oxidative stress-mediated expression of myostatin and atrogin-12016
Author(s)
Enoki Y, Watanabe H, Arake R, Sugimoto R, Imafuku T, Tominaga Y, Ishima Y, Kotani S, Nakajima M, Tanaka M, Matsushita K, Fukagawa M, Otagiri M, Maruyama T
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 32084-32084
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Effect of a Ferric Citrate Formulation, a Phosphate Binder, on Oxidative Stress in Chronic Kidney Diseases-Mineral and Bone Disorder Patients Receiving Hemodialysis: A Pilot Study2016
Author(s)
Tanaka M, Miyamura S, Imafuku T, Tominaga Y, Maeda H, Anraku M, Yamasaki K, Kadowaki D, Ishima Y, Watanabe H, Okuda T, Itoh K, Matsushita K, Fukagawa M, Otagiri M, Maruyama T
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 39
Issue: 6
Pages: 1000-1006
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] The clinical significance of plasma neopterin in heart failure with preserved left ventricular ejection fraction2016
Author(s)
Yamamoto E, Hirata Y, Tokitsu T, Kusaka H, Tabata N, Tsujita K, Yamamuro M, Kaikita K, Watanabe H, Hokimoto S, Maruyama T, Ogawa H
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Journal Title
ESC Heart Failure
Volume: 3
Pages: 53-59
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Comparison of Posttranslational Modification and the Functional Impairment of Human Serum Albumin in Commercial Preparations2016
Author(s)
Miyamura S, Imafuku T, Anraku M, Taguchi K, Yamasaki K, Tominaga Y, Maeda H, Ishima Y, Watanabe H, Otagiri M, Maruyama T
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Journal Title
J Pharm Sci
Volume: 105
Pages: 1043-1049
Related Report
Peer Reviewed / Acknowledgement Compliant
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