Elucidation of regulatory mechanism of WNK signal by protein degradation system

• Project/Area Number: 16H05314
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SOHARA Eisei 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (90510355)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: WNKキナーゼ / 塩分感受性高血圧 / 蛋白分解系 / 塩分感受性 / メトホルミン / 骨格筋 / 偽性低アルドステロン症２型 / PKA / AMPK / 高血圧

Outline of Final Research Achievements

Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, kelch-like 3 (KLHL3), and cullin3 (CUL3) genes are known to cause the hereditary disease pseudohypoaldosteronism type II (PHAII). In this project, we generated Cul3 knock-in PHAII model mice and KLHL3-/- mice. KLHL3-/- mice showed PHAII-like phenotypes, whereas KLHL3+/- mice did not. We further demonstrated that the dimerization of KLHL3 can explain this dominant negative effect. We also found that KLHL3 expression was decreased in CUL3WT/Δex9 mice. These findings indicate that the decreased abundance of KLHL3 is a specific phenomenon caused by mutant CUL3 (Δexon9). In this study, we clarified WNK kinase degradation system by KLHL3 and Cullin3. We have also investigated the function of WNK kinase in the organ other than kidney, and found that WNK4 is an adipogenic factor and its deletion reduces diet-Induced obesity in mice.

Academic Significance and Societal Importance of the Research Achievements

本研究により、遺伝性高血圧疾患において新規に発見されたKLHL3とCullin3によるWNK分解系を転写からリン酸化蛋白修飾まで幅広い新規機序を明らかにすることができた。特に、KLHL2/3,Cullin3遺伝子改変マウスの作成により本制御系の破綻がもたらす病態を明らかにした。さらに研究を発展させ、遺伝子改変マウス等を駆使して様々な臓器や病態での新たなWNKシグナルの機能探求を明らかにし、WNKキナーゼの新規の基質や下流分子を同定しており、今後、臨床への発展も目指していきたい。

Research Products

• [Journal Article] Genotype-Clinical Correlations in Polycystic Kidney Disease with No Apparent Family History (2019)
  • Author(s): Sekine Akinari、Fujimaru Takuya、Hoshino Junichi、Suwabe Tatsuya、Oguro Masahiko、Mizuno Hiroki、Kawada Masahiro、Sumida Keiichi、Hiramatsu Rikako、Chiga Motoko、Kikuchi Hiroaki、Ando Fumiaki、Mori Takayasu、Sohara Eisei、Uchida Shinichi、Sawa Naoki、Takaichi Kenmei、Ubara Yoshifumi
  • Journal Title: American Journal of Nephrology Volume: 49 Issue: 3 Pages: 233-240
  • DOI: 10.1159/000497444
  • Peer Reviewed
• [Journal Article] Failure to sense energy depletion may be a novel therapeutic target in chronic kidney disease (2019)
  • Author(s): Kikuchi H, Sasaki E, Nomura N, Mori T, Minamishima YA, Yoshizaki Y, Takahashi N, Furusho T, Arai Y, Mandai S, Yamashita T, Ando F, Maejima Y, Isobe K, Okado T, Rai T, Uchida S, Sohara E
  • Journal Title: Kidney international Volume: 95 Issue: 1 Pages: 123-137
  • DOI: 10.1016/j.kint.2018.08.030
  • Peer Reviewed
• [Journal Article] WNK1 regulates skeletal muscle cell hypertrophy by modulating the nuclear localization and transcriptional activity of FOXO4 (2018)
  • Author(s): Mandai S, Mori T, Nomura N, Furusho T, Arai Y, Kikuchi H, Sasaki E, Sohara E, Rai T, Uchida S
  • Journal Title: Scientific reports Volume: 8 Issue: 1 Pages: 9101-9101
  • DOI: 10.1038/s41598-018-27414-0
  • Peer Reviewed / Open Access
• [Journal Article] Decreased KLHL3 expression is involved in the pathogenesis of pseudohypoaldosteronism type II caused by cullin 3 mutation in vivo (2018)
  • Author(s): Yoshida S, Araki Y, Mori T, Sasaki E, Kasagi Y, Isobe K, Susa K, Inoue Y, Bomont P, Okado T, Rai T, Uchida S, Sohara E
  • Journal Title: Clinical and experimental nephrology Volume: 22 Issue: 6 Pages: 1251-1257
  • DOI: 10.1007/s10157-018-1593-z
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus (2018)
  • Author(s): Ando Fumiaki、Mori Shuichi、Yui Naofumi、Morimoto Tetsuji、Nomura Naohiro、Sohara Eisei、Rai Tatemitsu、Sasaki Sei、Kondo Yoshiaki、Kagechika Hiroyuki、Uchida Shinichi
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 1411-1411
  • DOI: 10.1038/s41467-018-03771-2
  • Peer Reviewed / Open Access
• [Journal Article] Kidney enlargement and multiple liver cyst formation implicate mutations in PKD1/2 in adult sporadic polycystic kidney disease (2018)
  • Author(s): Fujimaru T.、Mori T.、Sekine A.、Mandai S.、Chiga M.、Kikuchi H.、Ando F.、Mori Y.、Nomura N.、Iimori S.、Naito S.、Okado T.、Rai T.、Hoshino J.、Ubara Y.、Uchida S.、Sohara E.
  • Journal Title: Clinical Genetics Volume: 印刷中 Issue: 1 Pages: 125-131
  • DOI: 10.1111/cge.13249
  • Peer Reviewed
• [Journal Article] Metformin increases urinary sodium excretion by reducing phosphorylation of the sodium-chloride cotransporter (2018)
  • Author(s): Hashimoto Hiroko、Nomura Naohiro、Shoda Wakana、Isobe Kiyoshi、Kikuchi Hiroaki、Yamamoto Kouhei、Fujimaru Takuya、Ando Fumiaki、Mori Takayasu、Okado Tomokazu、Rai Tatemitsu、Uchida Shinichi、Sohara Eisei
  • Journal Title: Metabolism Volume: 85 Pages: 23-31
  • DOI: 10.1016/j.metabol.2018.02.009
  • Peer Reviewed
• [Journal Article] Role of ClC-K and barttin in low potassium-induced sodium chloride cotransporter activation and hypertension in mouse kidney (2018)
  • Author(s): Nomura Naohiro、Shoda Wakana、Wang Yuanlong、Mandai Shintaro、Furusho Taisuke、Takahashi Daiei、Zeniya Moko、Sohara Eisei、Rai Tatemitsu、Uchida Shinichi
  • Journal Title: Bioscience Reports Volume: 38 Issue: 1 Pages: 20171243-1243
  • DOI: 10.1042/bsr20171243
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Calcineurin inhibitors block sodium-chloride cotransporter dephosphorylation in response to high potassium intake. (2017)
  • Author(s): Shoda W, Nomura N, Ando F, Mori Y, Mori T, Sohara E, Rai T, Uchida S.
  • Journal Title: Kidney Int. Volume: 91 Issue: 2 Pages: 402-411
  • DOI: 10.1016/j.kint.2016.09.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] KLHL3 Knockout Mice Reveal the Physiological Role of KLHL3 and the Pathophysiology of Pseudohypoaldosteronism Type II Caused by Mutant KLHL3. (2017)
  • Author(s): Sasaki E, Susa K, Mori T, Isobe K, Araki Y, Inoue Y, Yoshizaki Y, Ando F, Mori Y, Mandai S, Zeniya M, Takahashi D, Nomura N, Rai T, Uchida S, Sohara E.
  • Journal Title: Mol Cell Biol. Volume: 27 Issue: 7 Pages: 1-13
  • DOI: 10.1128/mcb.00508-16
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Loop diuretics affect skeletal myoblast differentiation and exercise-induced muscle hypertrophy. (2017)
  • Author(s): Mandai S, Furukawa S, Kodaka M, Hata Y, Mori T, Nomura N, Ando F, Mori Y, Takahashi D, Yoshizaki Y, Kasagi Y, Arai Y, Sasaki E, Yoshida S, Furuichi Y, Fujii NL, Sohara E, Rai T, Uchida S.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 46369-46369
  • DOI: 10.1038/srep46369
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Salt suppresses IFNγ inducible chemokines through the IFNγ-JAK1-STAT1 signaling pathway in proximal tubular cells. (2017)
  • Author(s): Arai Y, Takahashi D, Asano K, Tanaka M, Oda M, Ko SBH, Ko MSH, Mandai S, Nomura N, Rai T, Uchida S, Sohara E.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 46580-46580
  • DOI: 10.1038/srep46580
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Impaired degradation of medullary WNK4 in the kidneys of KLHL2 knockout mice. (2017)
  • Author(s): Kasagi Y, Takahashi D, Aida T, Nishida H, Nomura N, Zeniya M, Mori T, Sasaki E, Ando F, Rai T, Uchida S, Sohara E.
  • Journal Title: Biochem Biophys Res Commun. Volume: 487 Issue: 2 Pages: 368-374
  • DOI: 10.1016/j.bbrc.2017.04.068
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Drug-Repositioning Screening for Keap1-Nrf2 Binding Inhibitors using Fluorescence Correlation Spectroscopy (2017)
  • Author(s): Yoshizaki Yuki、Mori Takayasu、Ishigami-Yuasa Mari、Kikuchi Eriko、Takahashi Daiei、Zeniya Moko、Nomura Naohiro、Mori Yutaro、Araki Yuya、Ando Fumiaki、Mandai Shintaro、Kasagi Yuri、Arai Yohei、Sasaki Emi、Yoshida Sayaka、Kagechika Hiroyuki、Rai Tatemitsu、Uchida Shinichi、Sohara Eisei
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 3945-3945
  • DOI: 10.1038/s41598-017-04233-3
  • Peer Reviewed / Open Access
• [Journal Article] WNK4 is indispensable for the pathogenesis of pseudohypoaldosteronism type II caused by mutant KLHL3 (2017)
  • Author(s): Susa Koichiro、Sohara Eisei、Takahashi Daiei、Okado Tomokazu、Rai Tatemitsu、Uchida Shinichi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 491 Issue: 3 Pages: 727-732
  • DOI: 10.1016/j.bbrc.2017.07.121
  • Peer Reviewed
• [Journal Article] Comprehensive genetic testing approach for major inherited kidney diseases, using next-generation sequencing with a custom panel (2017)
  • Author(s): Mori T, Hosomichi K, Chiga M, Mandai S, Nakaoka H, Sohara E, Okado T, Rai T, Sasaki S, Inoue I, Uchida S.
  • Journal Title: Clin Exp Nephrol. Volume: 印刷中 Issue: 1 Pages: 63-75
  • DOI: 10.1007/s10157-016-1252-1
  • Peer Reviewed / Open Access
• [Journal Article] WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice. (2017)
  • Author(s): Takahashi D, Mori T, Sohara E, Tanaka M, Chiga M, Inoue Y, Nomura N, Zeniya M, Ochi H, Takeda S, Suganami T, Rai T, Uchida S.
  • Journal Title: EBioMedicine Volume: 18 Pages: 118-27
  • DOI: 10.1016/j.ebiom.2017.03.011
  • Peer Reviewed / Open Access
• [Journal Article] Wnt5a induces renal AQP2 expression by activating calcineurin signalling pathway. (2016)
  • Author(s): Ando F, Sohara E, Morimoto T, Yui N, Nomura N, Kikuchi E, Takahashi D, Mori T, Vandewalle A, Rai T, Sasaki S, Kondo Y, Uchida S.
  • Journal Title: Nat Commun. Volume: 7 Issue: 1 Pages: 13636-13636
  • DOI: 10.1038/ncomms13636
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effects of diuretics on sodium-dependent glucose cotransporter 2 inhibitor-induced changes in blood pressure in obese rats suffering from the metabolic syndrome. (2016)
  • Author(s): Rahman A, Kittikulsuth W, Fujisawa Y, Sufiun A, Rafiq K, Hitomi H, Nakano D, Sohara E, Uchida S, Nishiyama A.
  • Journal Title: J Hypertens. Volume: 34 Issue: 5 Pages: 893-906
  • DOI: 10.1097/hjh.0000000000000871
  • Peer Reviewed
• [Presentation] 多発性嚢胞腎診療の新しい展望~ゲノムから薬剤治療まで~. (2018)
  • Author(s): 蘇原 映誠
  • Organizer: 第 48 回日本腎臓学会東部学術大会
  • Invited
• [Presentation] WNK シグナルが明らかにした塩分感受性高血圧のメカニズム. (2018)
  • Author(s): 蘇原 映誠
  • Organizer: 第 54 回高血圧関連疾患モデル学会学術総会
  • Invited
• [Presentation] ゲノムから解くADPKD: 嚢胞性腎疾患の網羅的遺伝子解析システムの開発と応用 (2018)
  • Author(s): 蘇原 映誠, 森 崇寧, 藤丸 拓也, 内田 信一.
  • Organizer: 第 61 回日本腎臓学会学術総会.
  • Invited
• [Presentation] AKAPs-PKA Disruptors Robustly Increase AQP2 Activity Independently of Vasopressin. (2018)
  • Author(s): Ando F, Yui N, Nomura N, Sohara E, Rai T, Sasaki S, Uchida S.
  • Organizer: ASN Kidney Week 2018.
  • Int'l Joint Research
• [Presentation] WNK1 suppresses LPS-induced cytokine production in macrophage (2018)
  • Author(s): Arai Y, Sohara E, Asano K, Tanaka M, Nomura N, Rai T, Uchida S.
  • Organizer: ISN Frontiers Meetings 2018.
  • Int'l Joint Research
• [Presentation] Genomic Background of Adults with Suspected Ciliopathy on Renal Biopsy. (2018)
  • Author(s): Fujimaru T, Mori T, Mandai S, Chiga M, Kikuchi H, Ando F, Mori Y, Susa K, Isobe K, Iimori S, Nomura N, Naito S, Okado T, Rai T, Nagatsuji K, Nagahama K, Mishima E, Mochizuki T, Sekine A, Hoshino J, Ubara Y, Uchida S, Sohara E.
  • Organizer: ASN Kidney Week 2018.
  • Int'l Joint Research
• [Presentation] WNK1-SPAK-NCC signaling cascade is involved in salt sensitive hypertension induced by aristolochic acid nephropathy. (2018)
  • Author(s): Furusho T, Sohara E, Mandai S, Kikuchi H, Ando F, Zeniya M, Mori T, Nomura N, Rai T, Uchida S.
  • Organizer: ASN Kidney Week 2018.
  • Int'l Joint Research
• [Presentation] Metformin has natriuretic effects through reduction of the sodium-chrolide cotransporter phosphorylation. (2018)
  • Author(s): Hashimoto H, Nomura N, Shoda W, Isobe K, Kikuchi H, Yamamoto K, Fujimaru T, Ando F, Mori T, Okado T, Rai T, Uchida S, Sohara E.
  • Organizer: ASN Kidney Week 2018.
  • Int'l Joint Research
• [Presentation] Generation and Analysis of KLHL2 Knockout Mice. (2018)
  • Author(s): Kasagi Y, Takahashi D, Aida T, Nishida H, Nomura N, Zeniya M, Mori T, Sasaki E, Ando F, Rai T, Uchida S, Sohara E.
  • Organizer: ISN Frontiers Meetings 2018.
  • Int'l Joint Research
• [Presentation] Amelioration of Renal Fibrosis and Tubulointerstitial Damage in Fat-1 Transgenic CKD Mice by Compensation of Decreased Omega-3 Fatty Acids in the Kidney. (2018)
  • Author(s): Takahashi N, Kikuchi H, Ishihara T, Arita M, Furusho T, Ando F, Mori T, Isobe K, Susa K, Nomura N, Rai T, Uchida S, Sohara E
  • Organizer: ASN Kidney Week 2018.
  • Int'l Joint Research
• [Presentation] Decreased protein level of KLHL3 is involved in PHAII caused by CUL3 mutation. (2018)
  • Author(s): Yoshida S, Araki Y, Mori T, Sasaki E, Kasagi Y, Isobe K, Susa K, Inoue Y, Rai T, Uchida S，Sohara E.
  • Organizer: ISN Frontiers Meetings 2018
  • Int'l Joint Research
• [Presentation] 家族歴のない成人多発性腎嚢胞患者における網羅的遺伝子解析を用いた遺伝子診断と臨床所見の検討 (2018)
  • Author(s): 藤丸拓也, 森崇寧, 関根章成, 萬代新太郎, 千賀宗子, 菊池寛昭, 安藤史顕, 森雄太郎, 野村尚弘, 飯盛聡一郎, 内藤省太郎, 岡戸丈和, 頼建光, 星野純一, 乳原善文, 蘇原映誠, 内田信一
  • Organizer: 第28回バゾプレシン研究会
• [Presentation] Association between Body Mass Index and In-hospital Mortality in Emergently Hospitalized Dialysis-Independent CKD Patients; A Nationwide Retrospective Cohort Study in Japan (2018)
  • Author(s): Hiroaki Kikuchi, Eiichiro Kanda, Fumiaki Ando, Hidehiko Sato, Kiyoshi Isobe, Takayasu Mori, Soichiro Iimori, Naohiro Nomura, Shotaro Naito, Eisei Sohara, Tomokazu Okado, Shinichi Uchida, Kiyohide Fushimi and Tatemitsu Rai
  • Organizer: ISN Frontiers Meetings 2018
  • Int'l Joint Research
• [Presentation] Role of ClC-K and Barttin in Low-Potassium induced Sodium-Chloride Cotransporter Activation and Hypertension in Mouse Kidney (2018)
  • Author(s): Naohiro Nomura, Wakana Shoda, Yuanlong Wang, Daiei Takahashi, Moko Zeniya, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
  • Organizer: ISN Frontiers Meetings 2018
  • Int'l Joint Research
• [Presentation] Genomic diagnosis of adult polycystic kidney disease with no family history (2018)
  • Author(s): Takuya Fujimaru, Takayasu Mori, Akinari Sekine, Shintaro Mandai, Motoko Chiga, Hiroaki Kikuchi, Fumiaki Ando, Yutaro Mori, Naohiro Nomura, Soichiro Iimori, Shotaro Naito, Tomokazu Okado, Tatemitsu Rai, Junichi Hoshino, Yoshifumi Ubara, Shinichi Uchida, Eisei Sohara
  • Organizer: ISN Frontiers Meetings 2018
  • Int'l Joint Research
• [Presentation] 高カリウムはカリシニューリンを活性化しNa-Cl共輸送体(NCC)を脱リン酸化して尿中カリウム排泄を促進する. (2017)
  • Author(s): 正田若菜, 野村尚弘, 安藤史顕, 森雄太郎, 森崇寧, 蘇原映誠, 頼建光, 内田信一.
  • Organizer: 第27回バゾプレシン研究会.
• [Presentation] 多発性嚢胞腎におけるゲノム情報と環境因子のクロストーク. (2017)
  • Author(s): 蘇原 映誠.
  • Organizer: 第27回バゾプレシン研究会
  • Invited
• [Presentation] WNK-SPAKシグナル系阻害薬の開発とその可能性. (2017)
  • Author(s): 蘇原 映誠.
  • Organizer: 臨床高血圧フォーラム
  • Invited
• [Presentation] CIC-Kチャネルはカリウム摂取不足時のNCC活性化と血圧上昇に重要である (2017)
  • Author(s): 野村 尚弘, 正田 若菜, 高橋 大栄, 銭谷 慕子, 蘇原 映誠, 頼 建光, 内田 信一
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] WNK4は脂肪細胞分化の制御因子である (2017)
  • Author(s): 高橋大栄, 森崇寧, 蘇原映誠. 田中都, 千賀宗子, 井上佑一, 野村尚弘, 銭谷慕子, 越智広樹, 竹田秀, 菅波孝祥, 頼建光, 内田信一
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] ループ利尿薬はマウス骨格筋細胞分化および運動による筋肥大効果を抑制する (2017)
  • Author(s): 萬代新太郎, 古川晋, 小高愛未, 畑裕, 森崇寧, 野村尚弘, 蘇原映誠, 頼建光, 内田信一
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] 塩は近位尿細管細胞においてJAK/STAT系を介してIFNgamma関連ケモカインを抑制する (2017)
  • Author(s): 新井洋平, 蘇原映誠, 高橋大栄, 浅野謙一, 田中正人, 小田真由美、洪繁、洪実, 萬代新太郎, 野村尚弘, 頼建光, 内田信一
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] 次世代シークエンサーを用いた遺伝性腎疾患の解析 (2017)
  • Author(s): 蘇原映誠, 森崇寧, 内田信一.
  • Organizer: 第60回日本腎臓学会学術総会
  • Invited
• [Presentation] 変異CUL3によるPHAIIの発症にはKLHL3の発現低下が関与する (2017)
  • Author(s): 吉田紗矢香, 蘇原映誠, 荒木雄也, 笠木祐里, 佐々木絵美, 須佐紘一郎, 森崇寧, 井上佑一, 磯部清志, 頼建光, 内田信一
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] 次世代シークエンサーにおける嚢胞性腎疾患遺伝子診断パネルの構築 (2017)
  • Author(s): 藤丸拓也, 蘇原映誠, 森崇寧, 萬代新太郎, 千賀宗子, 菊池寛昭, 安藤史顕, 森雄太郎, 野村尚弘, 内藤省太郎, 岡戸丈和, _建光, 内田信一
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] 保存期慢性腎臓病患者におけるサルコペニアの危険因子の検討 (2017)
  • Author(s): 石川聖子, 内藤省太郎, 銭谷慕子, 高橋大栄, 佐藤英彦, 飯盛聡一郎, 野村尚弘, 蘇原映誠, 神田英一郎, 岡戸丈和, 頼建光, 内田信一.
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] KLHL2は腎臓でWNK4蛋白の分解を行う (2017)
  • Author(s): 笠木祐里,蘇原映誠,相田知海,高橋大栄,西田秀範,野村尚弘,銭谷慕子,森崇寧,佐々木絵美,安藤史顕,頼建光,内田信一
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] TTPでの血漿交換治療の施行回数と在院死亡についての検討 (2017)
  • Author(s): 佐藤英彦, 飯盛聡一郎, 銭谷慕子, 高橋大栄, 野村尚弘, 内藤省太郎, 蘇原映誠, 岡戸丈和, 内田信一, 伏見清秀, 頼建光
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] WNK1はマクロファージにおけるLPS誘導性サイトカイン産生を抑制する (2017)
  • Author(s): 新井洋平, 蘇原映誠, 浅野謙一, 田中正人, 頼建光, 内田信一
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] 新規腎線維化改善薬としてのbortezomibの検討 (2017)
  • Author(s): 銭谷慕子, 森崇寧, 油井直史, 野村尚弘, 千賀宗子, 高橋大栄, 蘇原映誠, 頼建光, 内田信一
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] WNK kinase signalling to cation chloride transporters (2017)
  • Author(s): Sohara Eisei
  • Organizer: Symposium, INTERNATIONAL UNION OF PHYSIOLOGICAL SCIENCE, 38th World Congress
  • Int'l Joint Research
• [Presentation] Pseudohypoaldosteronism (2017)
  • Author(s): Sohara Eisei
  • Organizer: 10th International Meeting of Pediatric Endocrinology
  • Int'l Joint Research
• [Presentation] WNK シグナルを介した新しい塩分感受性調節機構の解明 (2017)
  • Author(s): 蘇原 映誠.
  • Organizer: 第40回日本高血圧学会総会
  • Invited
• [Presentation] 遺伝性高血圧疾患からPrecision Medicineを考える (2017)
  • Author(s): 蘇原 映誠.
  • Organizer: 第40回日本高血圧学会総会
  • Invited
• [Presentation] Association between Body Mass Index and In-hospital Mortality in Emergently Hospitalized Dialysis-Independent CKD Patients; A Nationwide Retrospective Cohort Study in Japan (2017)
  • Author(s): Hiroaki Kikuchi, Eiichiro Kanda, Fumiaki Ando, Hidehiko Sato, Kiyoshi Isobe, Takayasu Mori, Soichiro Iimori, Naohiro Nomura, Shotaro Naito, Eisei Sohara, Tomokazu Okado, Shinichi Uchida, Kiyohide Fushimi and Tatemitsu Rai
  • Organizer: The 50th Annual Meeting of the American Society of Nephrology
  • Int'l Joint Research
• [Presentation] Role of ClC-K and Barttin in Low-Potassium induced Sodium-Chloride Cotransporter Activation and Hypertension in Mouse Kidney (2017)
  • Author(s): Naohiro Nomura, Wakana Shoda, Yuanlong Wang, Daiei Takahashi, Moko Zeniya, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
  • Organizer: The 50th Annual Meeting of the American Society of Nephrology
  • Int'l Joint Research
• [Presentation] Genomic background of adult polycystic kidney disease patients without a family history (2017)
  • Author(s): Takuya Fujimaru, Takayasu Mori, Akinari Sekine, Shintaro Mandai, Motoko Chiga, Hiroaki Kikuchi , Fumiaki Ando, Yutaro Mori, Naohiro Nomura, Shotaro Naito, Tomokazu Okado, Tatemitsu Rai, Junichi Hoshino, Yoshifumi Ubara, Shinichi Uchida, Eisei Sohara
  • Organizer: The 50th Annual Meeting of the American Society of Nephrology
  • Int'l Joint Research
• [Presentation] A High Salt Diet Suppressed CXCL9 and CXCL10 in Proximal Tubules through the IFNγ-JAK1-STAT1 Signaling Pathway (2017)
  • Author(s): Yohei Arai, Shinichi Uchida et al.
  • Organizer: The 50th Annual Meeting of the American Society of Nephrology
  • Int'l Joint Research
• [Presentation] Decreased protein expression of KLHL3 is involved in the pathogenesis of PHAII caused by CUL3 mutation in vivo. (2017)
  • Author(s): Sayaka Yoshida, Yuya Araki, Takayasu Mori, Emi Sasaki, Yuri Kasagi, Kiyoshi Isobe, Koichiro Susa, Yuichi Inoue, Tatemitsu Rai, Shinichi Uchida，Eisei Sohara.
  • Organizer: The 51th Annual Meeting of American Society of Nephrology.
  • Int'l Joint Research
• [Presentation] Generation and Analysis of KLHL2 Knockout Mice (2017)
  • Author(s): Yuri Kasagi, Daiei Takahashi, Tomomi Aida, Hidenori Nishida, Naohiro Nomura, Moko Zeniya, Takayasu Mori, Emi Sasaki, Fumiaki Ando, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
  • Organizer: The 50th Annual Meeting of the American Society of Nephrology
  • Int'l Joint Research
• [Presentation] WNK4 Deletion Inhibits Adipogenesis In Vitro and In Vivo (2017)
  • Author(s): Daiei Takahashi, Shinichi Uchida
  • Organizer: The 50th Annual Meeting of the American Society of Nephrology
  • Int'l Joint Research
• [Presentation] Development of a Customized Diagnostic Panel for Targeted Exome Sequencing of Polycystic Kidney Diseases. (2016)
  • Author(s): Fujimaru T, Mori T, Mandai S, Chiga M, Kikuchi H, Ando F, Mori Y, Nomura N, Naito S, Okado T, Rai T, Uchida S, Sohara E.
  • Organizer: The 49th Annual Meeting of American Society of Nephrology
  • Place of Presentation: Chicago（米国）
  • Int'l Joint Research
• [Presentation] Targeted Metabolomic Analysis of Kidney from the Subtotal Nephrectomy Mouse Model of Chronic Kidney Disease. (2016)
  • Author(s): Kikuchi H, Nomura N, Minamishima Y, Rai T, Uchida S, Sohara E.
  • Organizer: The 49th Annual Meeting of American Society of Nephrology
  • Place of Presentation: Chicago（米国）
  • Int'l Joint Research
• [Presentation] Generation of p62/SQSTM1 (p62) KO Cell Lines Using CRISPR/Cas9 -The Role of p62 on WNK1 Regulation by Changes of Extracellular Potassium Concentration (2016)
  • Author(s): Mori Y, Mandai S, Mori T, Sohara E, Rai T, Uchida S.
  • Organizer: The 49th Annual Meeting of American Society of Nephrology
  • Place of Presentation: Chicago（米国）
  • Int'l Joint Research
• [Presentation] Generation and Analysis of KLHL3 Knockout Mice. (2016)
  • Author(s): Sasaki E, Susa K, Mori T, Isobe K, Araki Y, Inoue Y, Rai T, Uchida S, Sohara E.
  • Organizer: The 49th Annual Meeting of American Society of Nephrology
  • Place of Presentation: Chicago（米国）
  • Int'l Joint Research
• [Presentation] Calcineurin Rapidly Dephosphorylates Sodium-ChlorideCotransporter in Response to High Potassium Intake. (2016)
  • Author(s): Shoda W, Nomura N, Ando F, Mori Y, Mori T, Sohara E, Rai T, Uchida S.
  • Organizer: The 49th Annual Meeting of American Society of Nephrology
  • Place of Presentation: Chicago（米国）
  • Int'l Joint Research
• [Presentation] WNK4 regulates adipocyte differentiation in 3T3-L1 cells. (2016)
  • Author(s): Takahashi D, Mori T, Sohara E, Chiga M, Inoue Y, Nomura N, Zeniya M, Rai T, Uchida S.
  • Organizer: The 49th Annual Meeting of American Society of Nephrology
  • Place of Presentation: Chicago（米国）
  • Int'l Joint Research
• [Presentation] Drug Repositioning Screening for Keap1-Nrf2 Binding Inhibitors Using Fluorescent Correlation Spectroscopy. (2016)
  • Author(s): Yoshizaki Y, Sohara E, Mori T, Kikuchi E, Takahashi D, Zeniya M, Araki Y, Mori Y, Ando F, Rai T, Uchida S.
  • Organizer: The 49th Annual Meeting of American Society of Nephrology
  • Place of Presentation: Chicago（米国）
  • Int'l Joint Research
• [Presentation] The proteasome inhibitor bortezomib attenuates renal fibrosis in mice. (2016)
  • Author(s): Zeniya M, Mori T, Yui N, Nomura N, Chiga M, Sohara E, Rai T, Uchida S.
  • Organizer: The 49th Annual Meeting of American Society of Nephrology
  • Place of Presentation: Chicago（米国）
  • Int'l Joint Research
• [Presentation] 次世代シークエンサーを用いた遺伝性腎疾患の解析 (2016)
  • Author(s): 蘇原映誠, 森崇寧, 内田信一
  • Organizer: 第４６回日本腎臓学会東部学術大会
  • Place of Presentation: 京王プラザホテル（東京都、新宿区）
  • Invited
• [Presentation] 次世代シークエンサー時代の高血圧研究の実際 (2016)
  • Author(s): 蘇原映誠
  • Organizer: 第３９回日本高血圧学会総会
  • Place of Presentation: 仙台国際センター（宮城県、仙台市）
  • Invited
• [Presentation] 腎性尿崩症治療を目指したAQP2 細胞内局在制御機構の解明. (2016)
  • Author(s): 蘇原映誠
  • Organizer: 第43回日本神経内分泌学会学術集会
  • Place of Presentation: アクトシティ浜松コングレスセンター（静岡県、浜松市）
  • Invited