低酸素シグナルが拓く生活習慣病の新しい病態制御

2016 Fiscal Year Annual Research Report

• Project Area: Oxygen biology: a new criterion for integrated understanding of life
• Project/Area Number: 26111003
• Research Institution: The University of Tokyo
• Principal Investigator: 南学 正臣 東京大学, 医学部附属病院, 教授 (90311620)
• Co-Investigator(Kenkyū-buntansha): 合田 亘人 早稲田大学, 理工学術院, 教授 (00245549) ; 武田 憲彦 東京大学, 医学部附属病院, 特任講師 (40422307)
• Project Period (FY): 2014-07-10 – 2019-03-31
• Keywords: 低酸素 / エネルギー / 炎症 / 線維化

Outline of Annual Research Achievements

生活習慣病では長期に渡る実質細胞の障害に引き続き、炎症・線維化などが起こり、組織の不適切なリモデリングが繰り返され、臓器障害が進展していく。本研究では、炎症・線維化などに特有な酸素リモデリングが原因となって実質細胞での酸素の需要と供給のバランスが崩れ臓器機能を低下させる機序の全容を解明することを目的として、研究を進めている。
低酸素により起こる長期的な線維化に、他の転写調節因子との相互作用およびヒストン修飾の変化が関与していることを解析し、その一部の結果を本領域の成果として論文発表した。
炎症局所は低酸素環境に陥っており、そこに集積するマクロファージ遊走において、HIF-1α-PDK1を介する解糖系代謝シフト(Active glycolysis)が重要であることを明らかにした。Active Glycolysisは、非がん細胞における新たな細胞内代謝リプログラミング機構であることが判った。これらの知見は、本領域の成果として論文発表した。
また、糖尿病の肝臓では代謝活性化による酸素消費が亢進し低酸素環境に陥る。肝臓のHIF-1が糖尿病病態に対して抑制的に作用すること、またその分子機構の1つとして肝臓から分泌されるヘパトカインのニューレグリン1がオートクラインあるいはパラクラインを介して、肝糖新生系酵素の遺伝子発現の主要な転写因子FOXO1のリン酸化による不活化を誘導することで肝臓の糖産生を抑制することを明らかにし、論文発表した。
飛田班と共同で、新規酸素分圧感知プローブの開発と改良を行っている。三浦班と共同でハダカデバネズミおよびマウス初代細胞の解析を行っている。ハダカデバネズミより単離した線維芽細胞は、マウス線維芽細胞と比較して、ミトコンドリア活性が低下していること、TCA回路における中心代謝産物が減少していることを確認した。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

低酸素により起こる他の転写調節因子との相互作用の解析を論文化し、更に長期的なヒストン修飾の変化に関する研究も順調に進んでおり、論文化に向けて解析を進めている。
生活習慣病の病態に関わるマクロファージ遊走における低酸素シグナルの新たな役割につき、その機構を解明し論文化することができた。現在、引き続きActive Glycolysisが心臓リモデリングにおいて果たしている役割につき解析を継続している。糖尿病の病態にかかわる肝臓の低酸素ストレス応答の役割についても、その分子機構の一端を明らかにし報告でき、これらの解析を通じて、いくつかの生体内の代謝制御にかかわる新しいヘパトカインの同定にも成功した。一方、生活習慣病の共通病態である臓器の異常な脂肪蓄積における低酸素ストレス応答の役割を解析するためのショウジョウバエを用いた新しい実験系の立ち上げに成功し、低酸素ストレス応答システムが臓器への脂肪沈着を抑制する作用を示すことを見いだした。ハダカデバネズミの解析においても、Mass spectrometryを用いた代謝物解析に併せて生化学的アプローチに着手している。いずれのプロジェクトについても、概ね順調に進行していると考えられる。

Strategy for Future Research Activity

マクロファージActive Glycolysisが心臓リモデリングにおいて果たしている役割について引き続き解析を進める。特にマクロファージHIF-1αシグナルが心肥大、心線維化を制御する機構につき、その分子機序を明らかにする。
飛田班と共同で、新規酸素分圧感知プローブの改良を進める。
ハダカデバネズミ、マウス線維芽細胞におけるミトコンドリア各complex活性、およびTCA回路活性を規定するCitrate synthase活性につき解析を行う。既に行っているメタボローム解析と併せて、ハダカデバネズミ特異的代謝プロセスを解明する。
新規ヘパトカインのニューレグリン1の病態機能解析を進めるとともに、HIF-1によるニュ－レグリン1遺伝子発現の制御機構の解明を目指す。また、他のヘパトカインの糖尿病に対する機能解析にも取り組む。一方、低酸素ストレス応答による脂肪蓄積抑制作用の分子機構について、遺伝子スクリーニングを進め、この応答にかかわる遺伝子の同定とその生物作用について解析を行う。さらに、炎症応答とHIF-1との関わりについて、特に自然免疫様T細胞に注目して解析に取り組む。

Research Products

• [Journal Article] Vascular adhesion protein-1 enhances neutrophil infiltration by generation of hydrogen peroxide in renal ischemia/reperfusion injury. (2017)
  • Author(s): Tanaka S, Tanaka T, Kawakami T, Takano H, Sugahara M, Saito H, Higashijima Y, Yamaguchi J, Inagi R, Nangaku M.
  • Journal Title: Kidney Int Volume: 印刷中 Pages: 印刷中
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• [Journal Article] Previous dropout from diabetic care as a predictor of patients' willingness to use mobile applications for self-management: A cross-sectional study. (2017)
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  • Peer Reviewed
• [Journal Article] Effects of Daprodustat, a Novel Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Anemia Management in Japanese Hemodialysis Subjects. (2017)
  • Author(s): Akizawa T, Tsubakihara Y, Nangaku M, Endo Y, Nakajima H, Kohno T, Imai Y, Kawase N, Hara K, Lepore J, Cobitz A.
  • Journal Title: Am J Nephrol Volume: 45 Pages: 127-135
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• [Journal Article] Mizoribine therapy combined with steroids and mizoribine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome. (2017)
  • Author(s): Saito T, Iwano M, Matsumoto K, Mitarai T, Yokoyama H, Yorioka N, Nishi S, Yoshimura A, Sato H, Ogahara S, Sasatomi Y, Kataoka Y, Ueda S, Koyama A, Maruyama S, Nangaku M, Imai E, Matsuo S, Tomino Y; Refractory Nephrotic Syndrome Study Group.
  • Journal Title: Clin Exp Nephrol Volume: 印刷中 Pages: 印刷中
  • Peer Reviewed
• [Journal Article] Urinary N-acetyl-β-glucosaminidase and eGFR may identify patients to be treated with immuno-suppression at diagnosis in idiopathic membranous nephropathy. (2017)
  • Author(s): Bazzi C, Usui T, Rizza V, Casellato D, Gallieni M, Nangaku M.
  • Journal Title: Nephrology Volume: 印刷中 Pages: 印刷中
  • DOI: doi: 10.1111/nep.12952
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• [Journal Article] Selective plasma exchange can reduce auto-antibodies in patients with bullous pemphigoid without affecting factor XIII and fibrinogen. (2017)
  • Author(s): Nasu K, Hanafusa N, Nangaku M.
  • Journal Title: J Clin Apher Volume: 印刷中 Pages: 印刷中
  • DOI: doi: 10.1002/jca.21513
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• [Journal Article] Impact of end-stage renal disease on hospital outcomes among patients admitted to intensive care units: A retrospective matched-pair cohort study. (2017)
  • Author(s): Iwagami M, Yasunaga H, Matsui H, Horiguchi H, Fushimi K, Noiri E, Nangaku M, Doi K.
  • Journal Title: Nephrology Volume: 印刷中 Pages: 印刷中
  • DOI: doi: 10.1111/nep.12830
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• [Journal Article] Development of quality indicators for care of chronic kidney disease in the primary care setting using electronic health data: a RAND-modified Delphi method. (2017)
  • Author(s): Fukuma S, Shimizu S, Niihata K, Sada KE, Yanagita M, Hatta T, Nangaku M, Katafuchi R, Fujita Y, Koizumi J, Koizumi S, Kimura K, Fukuhara S, Shibagaki Y.
  • Journal Title: Clin Exp Nephrol Volume: 印刷中 Pages: 印刷中
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• [Journal Article] Ulcerative colitis with hepatitis B virus infection treated successfully by granulocyte monocyte apheresis. (2017)
  • Author(s): Saito H, Hanafusa N, Kishikawa J, Noiri E, Sunami E, Ishihara S, Watanabe T, Nangaku M.
  • Journal Title: J Clin Apher Volume: 印刷中 Pages: 印刷中
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• [Journal Article] Type I neuregulin1α is a novel local mediator to suppress hepatic gluconeogenesis in mice. (2017)
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  • Journal Title: Sci Rep Volume: 7 Pages: 42959
  • DOI: doi: 10.1038/srep42959
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• [Journal Article] Distinct Metabolic Phenotypes within Non-small Cell 1 Lung Cancer Define Selective Vulnerability to Glycolytic Inhibition of Lung Squamous Cell Carcinoma. (2017)
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  • Journal Title: Nat Commun Volume: 印刷中 Pages: 印刷中
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• [Journal Article] Bevacizumab-related microvascular angina and its management with nicorandil. (2017)
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• [Journal Article] Cardiac Sarcoidosis Diagnosed by Incidental Lymph Node Biopsy. (2017)
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  • Journal Title: Int Heart J Volume: 58 Pages: 140-143
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• [Journal Article] Actin-binding protein coronin 1A controls osteoclastic bone resorption by regulating lysosomal secretion of cathepsin K. (2017)
  • Author(s): Ohmae S, Noma N, Toyomoto M, Shinohara M, Takeiri M, Fuji, Takemoto K, Iwaisako K, Fujita T, Takeda N, Kawatani M, Aoyama M, Hagiwara M, Ishihama Y, Asagiri M.
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• [Journal Article] Planimetry of the orifice area in aortic valve stenosis using phase-contrast cardiac magnetic resonance imaging. (2017)
  • Author(s): Abe H., Iguchi N, Utanohara Y, Takada K, Hen Y, Machida H, Takeda N, Sumiyoshi T.
  • Journal Title: Int Heart J Volume: 印刷中 Pages: 印刷中
  • Peer Reviewed
• [Journal Article] Hypoxia-Inducible Factor-1α Activates the Transforming Growth Factor-β/SMAD3 Pathway in Kidney Tubular Epithelial Cells. (2016)
  • Author(s): Kushida N, Nomura S, Mimura I, Fujita T, Yamamoto S, Nangaku M, Aburatani H.
  • Journal Title: Am J Nephrol Volume: 44 Pages: 276-285
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• [Journal Article] Umbilical Cord Blood Transplantation-associated Nephrotic Syndrome Successfully Treated by Low-density Lipoprotein Apheresis. (2016)
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  • Journal Title: Intern Med Volume: 55 Pages: 2831-2836
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• [Journal Article] Impact of clinical context on acute kidney injury biomarker performances: differences between neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding protein. (2016)
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  • Journal Title: Sci Rep Volume: 6 Pages: 33077
  • DOI: doi: 10.1038/srep33077
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• [Journal Article] Analysis of the V2 Vasopressin Receptor (V2R) Mutations Causing Partial Nephrogenic Diabetes Insipidus Highlights a Sustainable Signaling by a Non-peptide V2R Agonist. (2016)
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  • Journal Title: J Biol Chem Volume: 291 Pages: 22460-22471
  • Peer Reviewed
• [Journal Article] DialBetics: Smartphone-Based Self-Management for Type 2 Diabetes Patients on Insulin Injections. (2016)
  • Author(s): Waki K, Fujiu K, Hayashi A, Kimura S, Kobayashi H, Nangaku M, Kadowaki T, Ohe K.
  • Journal Title: J Diabetes Sci Technol Volume: 10 Pages: 804-805
  • DOI: doi: 10.1177/1932296815619638
  • Peer Reviewed / Open Access
• [Journal Article] Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation. (2016)
  • Author(s): Okubo K, Kamiya M, Urano Y, Nishi H, Herter JM, Mayadas T, Hirohama D, Suzuki K, Kawakami H, Tanaka M, Kurosawa M, Kagaya S, Hishikawa K, Nangaku M, Fujita T, Hayashi M, Hirahashi J.
  • Journal Title: EBioMedicine Volume: 10 Pages: 204-215
  • DOI: doi: 10.1016/j.ebiom.2016.07.012.
  • Peer Reviewed / Open Access
• [Journal Article] Complete remission of thrombotic microangiopathy after treatment with eculizumab in a patient with non-Shiga toxin-associated bacterial enteritis: A case report. (2016)
  • Author(s): Omura T, Watanabe E, Otsuka Y, Yoshida Y, Kato H, Nangaku M, Miyata T, Oda S.
  • Journal Title: Medicine Volume: 95 Pages: e4104
  • DOI: doi: 10.1097/MD.0000000000004104
  • Peer Reviewed / Open Access
• [Journal Article] No association between dysplasminogenemia with p.Ala620Thr mutation and atypical hemolytic uremic syndrome. (2016)
  • Author(s): Miyata T, Uchida Y, Yoshida Y, Kato H, Matsumoto M, Kokame K, Fujimura Y, Nangaku M.
  • Journal Title: Int J Hematol Volume: 104 Pages: 223-227
  • Peer Reviewed
• [Journal Article] Potential Survival Benefit of Polymyxin B Hemoperfusion in Septic Shock Patients on Continuous Renal Replacement Therapy: A Propensity-Matched Analysis. (2016)
  • Author(s): Iwagami M, Yasunaga H, Noiri E, Horiguchi H, Fushimi K, Matsubara T, Yahagi N, Nangaku M, Doi K.
  • Journal Title: Blood Purif Volume: 42 Pages: 9-17
  • Peer Reviewed
• [Journal Article] Erythropoietin concentration in acute kidney injury is associated with insulin-like growth factor-binding protein-1. (2016)
  • Author(s): Yamashita T, Noiri E, Hamasaki Y, Matsubara T, Ishii T, Yahagi N, Nangaku M, Doi K.
  • Journal Title: Nephrology Volume: 21 Pages: 693-9
  • DOI: doi: 10.1111/nep.12656
  • Peer Reviewed
• [Journal Article] Association of Urinary Neutrophil Gelatinase-Associated Lipocalin With Long-Term Renal Outcomes in ICU Survivors: A Retrospective Observational Cohort Study. (2016)
  • Author(s): Isshiki R, Asada T, Sato D, Sumida M, Hamasaki Y, Inokuchi R, Matsubara T, Ishii T, Yahagi N, Nangaku M, Noiri E, Doi K.
  • Journal Title: Shock Volume: 46 Pages: 44-51
  • DOI: doi: 10.1097/SHK.0000000000000580.
  • Peer Reviewed
• [Journal Article] Interstitial renal fibrosis due to multiple cisplatin treatments is ameliorated by semicarbazide-sensitive amine oxidase inhibition. (2016)
  • Author(s): Katagiri D, Hamasaki Y, Doi K, Negishi K, Sugaya T, Nangaku M, Noiri E.
  • Journal Title: Kidney Int Volume: 89 Pages: 374-85
  • Peer Reviewed / Open Access
• [Journal Article] The reduced expression of proximal tubular transporters in acquired Fanconi syndrome with κ light chain deposition. (2016)
  • Author(s): Tojo A, Asaba K, Kinugasa S, Ikeda Y, Shintani Y, Fukayama M, Nangaku M.
  • Journal Title: Med Mol Morphol Volume: 49 Pages: 48-52
  • Peer Reviewed
• [Journal Article] Correction of Metabolic Alkalosis and Elevated Calcium Levels by Sodium Chloride in a Hemodialysis Patient With Inadequate Chloride Intake. (2016)
  • Author(s): Hirakawa Y, Hanafusa N, Nangaku M.
  • Journal Title: Ther Apher Dial Volume: 20 Pages: 86-87
  • DOI: doi: 10.1111/1744-9987.12335
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• [Journal Article] Impact of continuous renal replacement therapy intensity on septic acute kidney injury. (2016)
  • Author(s): Mayumi K, Yamashita T, Hamasaki Y, Noiri E, Nangaku M, Yahagi N, Doi K.
  • Journal Title: Shock Volume: 45 Pages: 133-138
  • DOI: doi: 10.1097/SHK.0000000000000496
  • Peer Reviewed
• [Journal Article] Rationale and study design of a randomized controlled trial to assess the effects of maintaining hemoglobin levels using darbepoetin alfa on prevention of development of end-stage kidney disease in non-diabetic CKD patients (PREDICT Trial). (2016)
  • Author(s): Imai E, Maruyama S, Nangaku M, Hirakata H, Hayashi T, Narita I, Kono H, Nakatani E, Morita S, Tsubakihara Y, Akizawa T.
  • Journal Title: Clin Exp Nephrol Volume: 20 Pages: 71-76
  • DOI: doi: 10.1007/s10157-015-1133-z
  • Peer Reviewed
• [Journal Article] High serum ALP level is associated with increased risk of denosumab-related hypocalcemia in patients with bone metastases from solid tumors. (2016)
  • Author(s): Kinoshita Y, Arai M, Ito N, Takashi Y, Makita N, Nangaku M, Shinoda Y, Fukumoto S.
  • Journal Title: Endocr J Volume: 63 Pages: 479-484
  • DOI: doi: 10.1507/endocrj.EJ16-0003
  • Peer Reviewed / Open Access
• [Journal Article] HIF-1α-PDK1 axis-induced active glycolysis plays an essential role in macrophage migratory capacity. (2016)
  • Author(s): Semba H, Takeda N, Isagawa T, Sugiura Y, Honda K, Wake M, Miyazawa H, Yamaguchi Y, Miura M, Jenkins D, Choi H, Kim JW, Asagiri M, Cowburn AS, Abe H, Soma K, Koyama K, Katoh M, Sayama K, Goda N, Johnson RS, Manabe I, Nagai R, Komuro I.
  • Journal Title: Nat Commun Volume: 7 Pages: 11635
  • DOI: doi: 10.1038/ncomms11635
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Karigane D, Kobayashi H, Morikawa T, Ootomo Y, Sakai M, Nagamatsu G, Kubota Y, Goda N, Matsumoto M, Nishimura EK, Soga T, Otsu K, Suematsu M, Okamoto S, Suda T, Takubo K. (2016)
  • Author(s): Karigane D, Kobayashi H, Morikawa T, Ootomo Y, Sakai M, Nagamatsu G, Kubota Y, Goda N, Matsumoto M, Nishimura EK, Soga T, Otsu K, Suematsu M, Okamoto S, Suda T, Takubo K.
  • Journal Title: Cell Stem Cell Volume: 19 Pages: 192-204
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• [Journal Article] The H3K9 methyltransferase Setdb1 regulates TLR4-mediated inflammatory responses in macrophages. (2016)
  • Author(s): Hachiya R, Shiihashi T, Shirakawa I, Iwasaki Y, Matsumura Y, Oishi Y, Nakayama Y, Miyamoto Y, Manabe I, Ochi K, Tanaka M, Goda N, Sakai J, Suganami T, Ogawa Y.
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• [Journal Article] Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles. (2016)
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• [Journal Article] Cardiogenic syncope possibly related to bevacizumab-containing combination chemotherapy for advanced non-small cell lung cancer. (2016)
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• [Journal Article] Atypical hemolytic uremic syndrome (aHUS): essential aspects of an accurate diagnosis. (2016)
  • Author(s): Laurence J, Haller H, Mannucci PM, Nangaku M, Praga M, Rodriguez de Cordoba S.
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  • Peer Reviewed / Int'l Joint Research
• [Journal Article] New insights into molecular mechanisms of epigenetic regulation in kidney disease. (2016)
  • Author(s): Mimura I, Tanaka T, Nangaku M.
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  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Progression after AKI: Understanding Maladaptive Repair Processes to Predict and Identify Therapeutic Treatments. (2016)
  • Author(s): Basile DP, Bonventre JV, Mehta R, Nangaku M, Unwin R, Rosner MH, Kellum JA, Ronco C; ADQI XIII Work Group.
  • Journal Title: J Am Soc Nephrol Volume: 27 Pages: 687-697
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  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Targeting Endogenous Repair Pathways after AKI. (2016)
  • Author(s): Humphreys BD, Cantaluppi V, Portilla D, Singbartl K, Yang L, Rosner MH, Kellum JA, Ronco C; Acute Dialysis Quality Initiative (ADQI) XIII Work Group.
  • Journal Title: J Am Soc Nephrol Volume: 27 Pages: 990-998
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  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inflammation in AKI: Current Understanding, Key Questions, and Knowledge Gaps. (2016)
  • Author(s): Rabb H, Griffin MD, McKay DB, Swaminathan S, Pickkers P, Rosner MH, Kellum JA, Ronco C; Acute Dialysis Quality Initiative Consensus XIII Work Group.
  • Journal Title: J Am Soc Nephrol Volume: 27 Pages: 371-379
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  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Therapeutic Targets of Human AKI: Harmonizing Human and Animal AKI. (2016)
  • Author(s): Okusa MD, Rosner MH, Kellum JA, Ronco C; Acute Dialysis Quality Initiative XIII Workgroup.
  • Journal Title: J Am Soc Nephrol Volume: 27 Pages: 44-48
  • DOI: doi: 10.1681/ASN.2015030233
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Renal Hemodynamics in AKI: In Search of New Treatment Targets. (2016)
  • Author(s): Matejovic M, Ince C, Chawla LS, Blantz R, Molitoris BA, Rosner MH, Okusa MD, Kellum JA, Ronco C; ADQI XIII Work Group.
  • Journal Title: J Am Soc Nephrol Volume: 27 Pages: 49-58
  • DOI: doi: 10.1681/ASN.2015030234
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Circadian clock and the onset of cardiovascular events. (2016)
  • Author(s): Takeda N, Maemura K.
  • Journal Title: Hypertens Res Volume: 39 Pages: 383-90
  • DOI: doi: 10.1038/hr.2016.9
  • Peer Reviewed
• [Presentation] 低酸素誘導性肺血管リモデリングにおける炎症細胞の役割 (2017)
  • Author(s): 武田憲彦
  • Organizer: 第9回日本生理学会大会
  • Place of Presentation: アクトシティ浜松、静岡
  • Year and Date: 2017-03-30
  • Invited
• [Presentation] The Role of Eosinophils in Pulmonary Arterial Remodelling (2017)
  • Author(s): 武田憲彦
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: ホテル日航金沢、金沢
  • Year and Date: 2017-03-17
  • Invited
• [Presentation] HIF-1alpha-PDK1 axis induced active glycolysis plays an essential role in macrophage migratory capacity. (2017)
  • Author(s): Takeda N.
  • Organizer: Keystone Symposium “Adaptaions to Hypoxia in Physiology and Disease”
  • Place of Presentation: Whistler Conference Centre, Whistler, British Columbia, Canada
  • Year and Date: 2017-03-09
  • Int'l Joint Research / Invited
• [Presentation] マクロファージ活性化における細胞内グルコース代謝の役割 (2016)
  • Author(s): 武田憲彦
  • Organizer: 第20回日本適応医学会学術集会
  • Place of Presentation: 東京コンベンションホール、東京
  • Year and Date: 2016-12-16
  • Invited
• [Presentation] Perivascular accumulation of M1 macrophages elicits the development of immature vascular formation. (2016)
  • Author(s): 武田憲彦
  • Organizer: 第24回日本血管生物医学会学術集会
  • Place of Presentation: 長崎ブリックホール、長崎
  • Year and Date: 2016-12-10
  • Invited
• [Presentation] Oxygen biology in the kidney. (2016)
  • Author(s): Nangaku M.
  • Organizer: 2nd NTU-UTokyo Joint Conference
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2016-12-01
  • Int'l Joint Research / Invited
• [Presentation] Novel therapeutic targets in PKD, DKD, and CKD: mitochondria, ER, and oxygen metabolism. (2016)
  • Author(s): Nangaku M.
  • Organizer: Yale University Nephrology Seminar
  • Place of Presentation: New Haven, USA
  • Year and Date: 2016-11-21
  • Invited
• [Presentation] Hypoxia-inducible factors in diabetic nephropathy. (2016)
  • Author(s): Nangaku M.
  • Organizer: 50th American Society of Nephrology
  • Place of Presentation: Chicago, USA
  • Year and Date: 2016-11-19
  • Int'l Joint Research / Invited
• [Presentation] 低酸素応答システムが拓く代謝性疾患の新しい病態理解 (2016)
  • Author(s): 合田亘人
  • Organizer: 第20回酸素ダイナミクス研究会
  • Place of Presentation: 東京
  • Year and Date: 2016-11-19
  • Invited
• [Presentation] HIF-1alpha-PDK1経路を介した代謝リプログラミングはマクロファージ遊走能を促進する (2016)
  • Author(s): 武田憲彦
  • Organizer: 第37回日本肥満学会
  • Place of Presentation: 東京ファッションタウン、東京
  • Year and Date: 2016-10-08
  • Invited
• [Presentation] Metabolic diseases and HIF-1 (2016)
  • Author(s): Goda N.
  • Organizer: 第89回生化学会大会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-09-26
  • Invited
• [Presentation] Switching of two HIF-alpha; isforms regulates inflammatory processes and cardiac remodeling (2016)
  • Author(s): 武田憲彦
  • Organizer: 第52回高血圧関連疾患モデル学会
  • Place of Presentation: 秋葉原UDX、東京
  • Year and Date: 2016-09-22
  • Invited
• [Presentation] Epigenetics of renal disease. (2016)
  • Author(s): Nangaku M.
  • Organizer: 15th Asian Pacific Congress of Nephrology
  • Place of Presentation: Perth, Australia
  • Year and Date: 2016-09-20
  • Int'l Joint Research / Invited
• [Presentation] Anemia management update. (2016)
  • Author(s): Nangaku M.
  • Organizer: 15th Asian Pacific Congress of Nephrology
  • Place of Presentation: Perth, Australia
  • Year and Date: 2016-09-17
  • Int'l Joint Research / Invited
• [Presentation] 心血管リモデリングにおける炎症細胞・低酸素シグナルの役割 (2016)
  • Author(s): 武田憲彦
  • Organizer: 第48回日本動脈硬化学会総会学術集会
  • Place of Presentation: 京王プラザホテル、東京
  • Year and Date: 2016-07-14
  • Invited
• [Presentation] HIF-1alpha-PDK1 axis induced active glycolysis plays an essential role in macrophage migratory capacity. (2016)
  • Author(s): Takeda N.
  • Organizer: 2016 HDRC International Symposium
  • Place of Presentation: Incheon, Korea
  • Year and Date: 2016-06-17
  • Int'l Joint Research / Invited
• [Presentation] Development of novel drugs targeting renal hypoxia and anaemia. (2016)
  • Author(s): Nangaku M.
  • Organizer: 53rd European Renal Association/European Dialysis and Transplantation Association
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2016-05-24
  • Int'l Joint Research / Invited
• [Presentation] Hypoxia and persistent inflammation in CKD. (2016)
  • Author(s): Nangaku M.
  • Organizer: XVIII International Congress on Nutrition and Metabolism in Renal Disease
  • Place of Presentation: Okinawa, Japan
  • Year and Date: 2016-04-22
  • Int'l Joint Research / Invited