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Metabolic Reprogramming and Hypoxic Memory in Kidney Disease

Research Project

Project/Area Number 15H04835
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

Nangaku Masaomi  東京大学, 医学部附属病院, 教授 (90311620)

Co-Investigator(Kenkyū-buntansha) 川上 貴久  東京大学, 医学部附属病院, 助教 (10722093)
稲城 玲子  東京大学, 医学部附属病院, 特任准教授 (50232509)
田中 哲洋  東京大学, 医学部附属病院, 講師 (90508079)
加藤 秀樹  東京大学, 医学部附属病院, 講師 (90625237)
正路 久美  東京大学, 医学部附属病院, 病院診療医 (00439423)
三村 維真理  東京大学, 医学部附属病院, 助教 (00727084)
和田 健彦  東海大学, 医学部, 准教授 (90447409)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords低酸素 / HIF / 慢性腎臓病 / 腎不全 / エネルギー代謝 / エピジェネティクス / 低酸素応答 / エピジェネティックス / 線維化 / エピジェネティック / HIF / エピゲノム
Outline of Final Research Achievements

Cultured tubular cells and endothelial cells exposed to hypoxia demonstrated changes in expression levels of genes related to energy metabolism and fibrosis. Fibrogenic responses by tubular cells cultured under hypoxic conditions are likely to be regulated by synergistic effects of transcriptional factors.
We developed a novel phosphorescence probe that allows accurate measurement of oxygen tensions of the kidney in vivo. We observed decreases in oxygen tensions in the kidney of animals with anemia or diabetes, and we also found hypoxia of the kidney after acute kidney injury leading to fibrosis. Furthermore, we improved this hypoxia-induced fibrosis after acute kidney injury by performing epigenetic interventions.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (52 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Open Access: 10 results,  Acknowledgement Compliant: 5 results) Presentation (38 results) (of which Int'l Joint Research: 28 results,  Invited: 27 results)

  • [Int'l Joint Research] Uppsala University(Sweden)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Genome-wide analysis revealed that DZNep reduces tubulointerstitial fibrosis via down-regulation of pro-fibrotic genes.2018

    • Author(s)
      Mimura I, Hirakawa Y, Kanki Y, Nakaki R, Suzuki Y, Tanaka T, Aburatani H, Nangaku M.
    • Journal Title

      Sci Rep.

      Volume: 28 Issue: 1 Pages: 3779-3779

    • DOI

      10.1038/s41598-018-22180-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Issue: 1 Pages: 154-164

    • DOI

      10.1016/j.kint.2017.01.014

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Renal Hypoxia in CKD; Pathophysiology and Detecting Methods.2017

    • Author(s)
      Hirakawa Y, Tanaka T, Nangaku M.
    • Journal Title

      Front Physiol

      Volume: 8 Pages: 99-99

    • DOI

      10.3389/fphys.2017.00099

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel lnc RNA regulated by HIF-1 inhibits apoptotic cell death in the renal tubular epithelial cells under hypoxia.2017

    • Author(s)
      Mimura I, Hirakawa Y, Kanki Y, Kushida N, Nakaki R, Suzuki Y, Tanaka T, Aburatani H, Nangaku M.
    • Journal Title

      Physiol Rep.

      Volume: 5 Issue: 8 Pages: e13203-e13203

    • DOI

      10.14814/phy2.13203

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic Changes in the Acute Kidney Injury-to-Chronic Kidney Disease Transition.2017

    • Author(s)
      Nangaku M, Hirakawa Y, Mimura I, Inagi R, Tanaka T.
    • Journal Title

      Nephron.

      Volume: 137 Issue: 4 Pages: 256-259

    • DOI

      10.1159/000476078

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Echinomycin inhibits adipogenesis in 3T3-L1 cells in a HIF-independent manner.2017

    • Author(s)
      Yamaguchi J, Tanaka T, Saito H, Nomura S, Aburatani H, Waki H, Kadowaki T, Nangaku M.
    • Journal Title

      Sci Rep.

      Volume: 26 Issue: 1 Pages: 6516-6516

    • DOI

      10.1038/s41598-017-06761-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prolyl hydroxylase domain inhibitors as a novel therapeutic approach against anemia in chronic kidney disease.2017

    • Author(s)
      Sugahara M, Tanaka T, Nangaku M.
    • Journal Title

      Kidney Int.

      Volume: 92 Issue: 2 Pages: 306-312

    • DOI

      10.1016/j.kint.2017.02.035

    • Related Report
      2017 Annual Research Report
    • 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

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] New insights into molecular mechanisms of epigenetic regulation in kidney disease.2016

    • Author(s)
      Mimura I, Tanaka T, Nangaku M.
    • Journal Title

      Clin Exp Pharmacol Physiol

      Volume: 43 Issue: 12 Pages: 1159-1167

    • DOI

      10.1111/1440-1681.12663

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Quantitating intracellular oxygen tension in vivo by phosphorescence lifetime measurement2015

    • Author(s)
      Hirakawa Y, Yoshihara T, Kamiya M, Mimura I, Fujikura D, Masuda T, Kikuchi R, Takahashi I, Urano Y, Tobita S, Nangaku M.
    • Journal Title

      Sci Rep

      Volume: 5 Issue: 1 Pages: 17838-17838

    • DOI

      10.1038/srep17838

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inflammation and hypoxia linked to renal injury by CCAAT/enhancer-binding protein δ2015

    • Author(s)
      Yamaguchi J, Tanaka T, Eto N, Nangaku M.
    • Journal Title

      Kidney International

      Volume: 印刷中 Issue: 2 Pages: 262-75

    • DOI

      10.1038/ki.2015.21

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sirtuin1 Maintains Actin Cytoskeleton by Deacetylation of Cortactin in Injured Podocytes.2015

    • Author(s)
      Motonishi S, Nangaku M, Wada T, Ishimoto Y, Ohse T, Matsusaka T, Kubota N, Shimizu A, Kadowaki T, Tobe K, Inagi R.
    • Journal Title

      J Am Soc Nephrol.

      Volume: 26・8 Issue: 8 Pages: 1939-59

    • DOI

      10.1681/asn.2014030289

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Anti-inflammatory role of DPP-4 inhibitors in a non-diabetic model of glomerular injury2015

    • Author(s)
      Higashijima Y, Tanaka T, Yamaguchi J, Tanaka S, Nangaku M
    • Journal Title

      Am J Physiol Renal Physiol

      Volume: ahead of print Issue: 8 Pages: F878-F887

    • DOI

      10.1152/ajprenal.00590.2014

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] From diabetic nephropathy to diabetic kidney disease2018

    • Author(s)
      Nangaku M.
    • Organizer
      The 16th Asian Pacific Congress of Nephrology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Epigenetic change in progression of AKI to CKD2018

    • Author(s)
      Nangaku M.
    • Organizer
      The 16th Asian Pacific Congress of Nephrology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Epigenetics and AKI-CKD transition.2017

    • Author(s)
      Nangaku M.
    • Organizer
      22nd International Conference on Advances in Critical Care: AKI & CRRT 2017
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 低酸素と腎障害2017

    • Author(s)
      南学正臣
    • Organizer
      第6回臨床高血圧フォーラム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] The role of HIF stabilizer in renal fibrosis2017

    • Author(s)
      Nangaku M.
    • Organizer
      The 37th Annual Meeting of the Korean Society of Nephrology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 新規貧血治療薬と今後の腎性貧血治療2017

    • Author(s)
      南学正臣
    • Organizer
      第62回透析医学会学術集会・総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Metabolic memory and hypoxic memory: epigenetics in diabetic nephropathy2017

    • Author(s)
      Nangaku M.
    • Organizer
      The 53rd Annual Meeting of the Australia/New Zealand Society of Nephrology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Epigenetics and CKD2017

    • Author(s)
      Nangaku M.
    • Organizer
      Nephrology and Transplantation Update Course of ANZSN/APSN CME
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Gene Expression Profiles of Glomeruli from BTBR ob/ob Mice Treated with Prolyl Hydroxylase Inhibitor Suggest Involvement of Extracellular Matrix Modulators in Pathogenesis of Diabetic Kidney Disease2017

    • Author(s)
      Sugahara M, Tanaka T, Tanaka S, Fukui K, Shimizu A, Ishimoto Y, Inagi R, Nangaku M.
    • Organizer
      The 51st Annual Meeting of the American Society of Nephrology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibition of Glycolysis Attenuates Ischemia-Reperfusion Injury via Metabolic and Redox Changes in Proximal Tubular Cells2017

    • Author(s)
      Shinohara A, Kawakami T, Nangaku M.
    • Organizer
      The 51st Annual Meeting of the American Society of Nephrology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibition of Prolyl Hydroxylase Domain (PHD) Reduces Glomerular Macrophage Infiltration and Improves Albuminuria in Mice with a High Fat Diet2017

    • Author(s)
      Saito H, Tanaka T, Sugahara M, Fukui K, Wakashima T, Nangaku M.
    • Organizer
      The 51st Annual Meeting of the American Society of Nephrology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Treatment of anemia in CKD and doping2017

    • Author(s)
      Nangaku M.
    • Organizer
      Cunio Richardson Lecture at University of Miami
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Anemia in CKD2017

    • Author(s)
      Nangaku M.
    • Organizer
      ISN/SRC CME course at Vietnam Society of Nephrology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Update of anemia management in CKD patients2017

    • Author(s)
      Nangaku M.
    • Organizer
      The 2nd International Congress of Chinese Nephrologists
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / 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
    • Related Report
      2016 Annual Research Report
    • 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 Unviersity Nephrology Seminar
    • Place of Presentation
      New Haven, USA
    • Year and Date
      2016-11-21
    • Related Report
      2016 Annual Research Report
    • 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
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Abnormal oxygen metabolism in the kidney.2016

    • Author(s)
      Nangaku M.
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-26
    • Related Report
      2016 Annual Research Report
    • 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
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Epigenetics of Renal Disease2016

    • Author(s)
      Nangaku M.
    • Organizer
      15th Asian Pacific Congress of Nephrology
    • Place of Presentation
      Perth, Australia
    • Year and Date
      2016-09-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 低酸素における炎症とepigenome.2016

    • Author(s)
      南学正臣
    • Organizer
      第16回日本抗加齢医学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-06-10
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Development of novel drugs targeting renal hypoxia and anaemia.2016

    • Author(s)
      Nangaku M.
    • Organizer
      53rd ERA/EDTA congress
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2016-05-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of novel drugs targeting renal hypoxia and anaemia2016

    • 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
    • Related Report
      2015 Annual Research Report
    • 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
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] りん光寿命測定を用いた腎臓尿細管細胞内分圧の測定2015

    • Author(s)
      平川陽亮、吉原利忠、神谷真子、三村維真理、田中真司、田中哲洋、浦野泰照、飛田成史、南学正臣
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] 低酸素とTGF-βは、下流にある IGFBP3 を介して、尿細管上皮細胞に apoptosis を誘導する.2015

    • Author(s)
      串田夏樹、野村征太郎、藤田隆教、三村維真理、南学正臣、油谷浩幸.
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Quantitating Intracellular Oxygen Tension in Kidney by Phosphorescence Lifetime Measurement.2015

    • Author(s)
      Yosuke Hirakawa, Imari Mimura, Toshitada Yoshihara, Mako Kamiya, Yasuteru Urano, Seiji Tobita, Masaomi Nangaku.
    • Organizer
      The 49th Annual Meeting of the American Society of Nephrology
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibition of Vascular Adhesion Protein-1 Suppresses Neutrophil Infiltration and Preserves Renal Function in the Rat Model of Renal Ischemia–Reperfusion Injury.2015

    • Author(s)
      Shinji Tanaka, Tetsuhiro Tanaka, Reiko Inagi, Masaomi Nangaku.
    • Organizer
      The 49th Annual Meeting of the American Society of Nephrology
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Oxidative Stres and Kidney Injury.2015

    • Author(s)
      Nangaku M.
    • Organizer
      The 49th Annual Meeting of the American Society of Nephrology
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2015-11-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Palmitate Exacerbates Renal Anemia: Suppression of Renal Erythropoietin Production via Endoplasmic Reticulum Stress.2015

    • Author(s)
      Reiko Inagi, Thitinun Anusornvongchai, Yu Ishimoto, Akira Okada, Norio Suzuki, Masayuki Yamamoto, Masaomi Nangaku.
    • Organizer
      The 49th Annual Meeting of the American Society of Nephrology
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2015-11-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sodium-glucose cotransporter 2 inhibition ameliorates glomerular hyperfiltration without affecting renal/glomerular hypertrophy in a mouse model of type 2 diabetes.2015

    • Author(s)
      Tanaka S, Tanaka T, Inagi R, Nangaku M.
    • Organizer
      Keystone Symposia: Diabetes: New insights into molecular mechanisms and therapeutic strategies.
    • Place of Presentation
      ウエスティン都ホテル京都(京都府京都市)
    • Year and Date
      2015-10-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Estimation of intracellular oxygen concentration in diabetic kidney by phosphorescence lifetime measurement.2015

    • Author(s)
      Hirakawa Y, Mimura I, Yoshihara T, Kamiya M, Tanaka S, Tanaka T, Inagi R, Urano Y, Tobita S, Nangaku M.
    • Organizer
      Keystone Symposia: Diabetes: New insights into molecular mechanisms and therapeutic strategies.
    • Place of Presentation
      ウエスティン都ホテル京都(京都府京都市)
    • Year and Date
      2015-10-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Palmitate suppresses EPO production via ER stress in renal EPO producing cells.2015

    • Author(s)
      Anusomvongchai T, Tanaka S, Hirakawa Y, Suzuki n, Yamamoto M, Nangaku M, Inagi R.
    • Organizer
      Keystone Symposia: Diabetes: New insights into molecular mechanisms and therapeutic strategies.
    • Place of Presentation
      ウエスティン都ホテル京都(京都府京都市)
    • Year and Date
      2015-10-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腎不全に至る共通経路と高血圧の役割2015

    • Author(s)
      南学正臣
    • Organizer
      第38回日本高血圧学会総会
    • Place of Presentation
      愛媛県県民文化会館(愛媛県松山市)
    • Year and Date
      2015-10-11
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] AKI-to-CKD: epidemiology and pathogenesis2015

    • Author(s)
      Nangaku M.
    • Organizer
      Shanghai International AKI-CRRT Forum
    • Place of Presentation
      Shanghai, China
    • Year and Date
      2015-07-04
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 腎性貧血とHIF2015

    • Author(s)
      南学正臣
    • Organizer
      第60回日本透析医学会学術集会
    • Place of Presentation
      パシフィコ横浜国際会議場(神奈川県横浜市)
    • Year and Date
      2015-06-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Hypoxia as a new therapeutic target in CKD2015

    • Author(s)
      南学正臣
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-06-06
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Development of novel drugs targeting CKD: hypoxia, oxidative stress, and epigenetics2015

    • Author(s)
      Nangaku M.
    • Organizer
      52nd European Renal Association/European Dialysis and Transplantation Association
    • Place of Presentation
      London, UK
    • Year and Date
      2015-05-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2015-04-16   Modified: 2019-03-29  

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