Disease specific therapy of polycystic kidney disease based on its pathophysiology considering the ubiquitin-proteasome proteolysis mechanism

• Project/Area Number: 23591580
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Wakayama Medical University
• Principal Investigator: NAKANISHI Koichi 和歌山県立医科大学, 医学部, 講師 (50336880)
• Co-Investigator(Kenkyū-buntansha): YOSHIKAWA Norishige 和歌山県立医科大学, 医学部, 教授 (10158412)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 多発性嚢胞腎 / CPKマウス / ユビキチン・プロテアソーム / 上皮間葉移行(EMT) / 疾患特異的治療

Research Abstract

Polycystic kidney disease is an inherited disease, which is the most frequent in our country, and is one of main causes of chronic renal failure. There are two types of polycystic kidney disease, autosomal dominant (ADPKD) and autosomal recessive (ARPKD).
In this study, we elucidated ubiquitin-proteasome proteolysis mechanism in multiple pathophysiology of polycystic kidney disease, and aimed to confirm the effect with modification of ubiquitin-proteasome proteolysis using the model animal for disease specific therapy development based on the pathophysiology of polycystic kidney disease to adapt it to human. We focused on ubiquitin E3 ligase family, Smurf1 and Smurf2.

Research Products

• [Journal Article] Telmisartan ameliorates fibrocystic liver disease in an orthologous rat model of human autosomal recessive polycystic kidney disease. (2013)
  • Author(s): Yoshihara D, Kugita M, Sasaki M, Horie S, Nakanishi K, Abe T, Aukema HA, Yamaguchi T, Nagao S.
  • Journal Title: PLoS One Volume: 8 Issue: 12 Pages: e81480-e81480
  • DOI: 10.1371/journal.pone.0081480
  • Peer Reviewed
• [Journal Article] 繊毛病(Ciliopathy) (2012)
  • Author(s): 中西浩一,吉川徳茂
  • Journal Title: 日本小児腎臓病学会雑誌 Volume: 25(2) Pages: 127-131
  • Peer Reviewed
• [Journal Article] 常染色体劣性多発性嚢胞腎-疫学と臨床.特集:多発性嚢胞腎 (2012)
  • Author(s): 中西浩一,吉川徳茂,服部元史
  • Journal Title: 腎臓 Volume: 34(3) Pages: 194-200
• [Journal Article] ARPKDの基礎と臨床-最新の知見特集:多発性嚢胞腎-最新の知見と今後の課題 (2012)
  • Author(s): 中西浩一,吉川徳茂
  • Journal Title: 日本腎臓学会誌 Volume: 54(4) Pages: 534-537
• [Journal Article] 多発性嚢胞腎診療指針 (2011)
  • Author(s): 乳原善文, 香村衡一, 木村理, 嶋村剛, 田邉一成, 土谷健, 成田一衛, 中西浩一, 西尾妙織, 奴田原紀久雄, 野村信介, 花岡一成, 東原英二, 堀江重郎, 武藤智, 望月俊雄
  • Journal Title: 日本腎臓学会誌 Volume: 53 Pages: 556-583
  • NAID: 10029736800
• [Journal Article] 進行性腎障害に関する調査研究班多発性嚢胞腎分科会厚生労働省進行性腎障害調査研究班多発性嚢胞腎診療指針2010年8月(解説) (2010)
  • Author(s): 乳原善文,香村衡一,木村理,嶋村剛,田邉一成,土谷健,成田一衛,中西浩一,西尾妙織,奴田原紀久雄,野村信介,花岡一成,東原英二,堀江重郎,武藤智,望月俊雄
  • Journal Title: 日本腎臓学会誌 Volume: 53 Pages: 556-583
  • Peer Reviewed
• [Presentation] 常染色体劣性多発性嚢胞腎の鑑別を要した3例 (2013)
  • Author(s): 浜武継,中西浩一,佐藤匡,向山弘展,戸川寛子,島友子,辻本弘,神波信次,吉川徳茂
  • Organizer: 第35回日本小児腎不全学会学術集会
  • Place of Presentation: 郡山
  • Year and Date: 2013-10-24
• [Presentation] cpkマウスARPKDモデルにおける病的Smad3リン酸化 (2013)
  • Author(s): 浜武継,中西浩一,向山弘展,戸川寛子,佐藤匡,島友子,宮嶋正康,野津寛大,高橋久英,長尾枝澄香,飯島一誠,吉川徳茂
  • Organizer: 第21回嚢胞性腎疾患研究会
  • Place of Presentation: 東京
  • Year and Date: 2013-09-21
• [Presentation] cpkマウスにおける病的態・遺伝子診断小児嚢胞性腎疾患の病Smad3リン酸化 (2013)
  • Author(s): 浜武継,中西浩一,向山弘展,戸川寛子,佐藤匡,島友子,宮嶋正康,野津寛大,高橋久英,長尾枝澄香,飯島一誠,吉川徳茂
  • Organizer: 第22回発達腎研究会
  • Place of Presentation: 高槻
  • Year and Date: 2013-09-14
• [Presentation] 遺伝性腎疾患のABC (2013)
  • Author(s): 中西浩一
  • Organizer: 第14回徳島県小児膠原病・腎疾患談話会
  • Place of Presentation: 徳島(特別講演)
  • Year and Date: 2013-04-10
• [Presentation] Smad3 Phosphorylated at Both Linker and COOH-Terminal Regions in Cyst-Lining Epithelia in cpk Mouse, a Model of ARPKD (2013)
  • Author(s): Hama T, Nakanishi K, Mukaiyama H, Togawa H, Sato M, Shima Y, Miyajima M, Nozu K, Nagao S, Takahashi H, Iijima K, Yoshikawa N
  • Organizer: 46^<th> Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Atlanta, USA(JASN 24:303A)
• [Presentation] Possible contribution of fibrocytes to renal fibrosis in cpk mouse, a model of ARPKD (2013)
  • Author(s): Hama T, Nakanishi K, Mukaiyama H, Sato M, Togawa H, Shima Y, Miyajima M, Takahashi H, Nagao S, Iijima K, Yoshikawa N
  • Organizer: 15th Congress of the International Pediatric Nephrology Association
  • Place of Presentation: Shanghai, China
• [Presentation] cpkマウス多発性嚢胞腎モデル腎線維化におけるfibrocyteの関与 (2013)
  • Author(s): 浜武継,中西浩一,向山弘展,佐藤匡,戸川寛子,島友子,宮嶋正康,高橋久英,長尾静子,飯島一誠,吉川徳茂
  • Organizer: 第48回日本小児腎臓病学会学術集会
  • Place of Presentation: 徳島
• [Presentation] Ciliopathy. Continuous Professional Development, Theme: Current Issues in Pediatric Nephrology. (2013)
  • Author(s): Nakanishi K
  • Organizer: The 11th Korea-Japan Pediatric Nephrology Seminar 2013
  • Place of Presentation: Seoul, Korea
  • Invited
• [Presentation] Possible contribution of fibrocytes to renal fibrosis in cpk mouse, a model of ARPKD. (2013)
  • Author(s): Hama T, Nakanishi K, Mukaiyama H, Sato M, Togawa H, Shima Y, Miyajima M, Takahashi H, Nagao S, Iijima K, Yoshikawa N&#61486;
  • Organizer: The 15th Congress of the International Pediatric Nephrology Association
  • Place of Presentation: Shanghai, China
• [Presentation] Smad3 Phosphorylated at Both Linker and COOH-Terminal Regions in Cyst-Lining Epithelia in cpk Mouse, a Model of ARPKD. (2013)
  • Author(s): Hama T, Nakanishi K, Mukaiyama H, Togawa H, Sato M, Shima Y, Miyajima M, Nozu K, Nagao S, Takahashi H, Iijima K, Yoshikawa N.
  • Organizer: The 46th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Atlanta, USA
• [Presentation] アルポート症候群と多発性嚢胞腎 (2012)
  • Author(s): 中西浩一
  • Organizer: 第11回弘前小児腎疾患フォーラム
  • Place of Presentation: 弘前(特別講演)
  • Year and Date: 2012-10-26
• [Presentation] 遺伝性ネフローゼ症候群と多発性嚢胞腎 (2012)
  • Author(s): 中西浩一
  • Organizer: 第22回北海道小児腎臓病研究会
  • Place of Presentation: 札幌(特別講演)
  • Year and Date: 2012-10-20
• [Presentation] Possible Contribution of Fibrocytes to Renal Fibrosis in Cpk Mouse, a Model of ARPKD (2012)
  • Author(s): Hama T, Nakanishi K, Mukaiyama H, Togawa H, Shima Y, Miyajima M, Takahashi H, Nagao S, Iijima K, Yoshikawa N
  • Organizer: 45^<th> Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego, USA(JASN 2012;23:596A)
• [Presentation] ARPKDの病因・病態の解明と診断・治療の進歩 (2012)
  • Author(s): 中西浩一
  • Organizer: 第34回日本小児腎不全学会学術集会
  • Place of Presentation: 洲本(シンポジウム,座長兼任)
• [Presentation] 繊毛病プロフェッショナル-5 (2012)
  • Author(s): 中西浩一
  • Organizer: 第47回日本小児腎臓病学会学術集会
  • Place of Presentation: 東京(教育講演)
• [Presentation] cpkマウスにおける部位特定的リン酸化Smad3の発現 (2012)
  • Author(s): 向山弘展,中西浩一,浜武継,戸川寛子,島友子,宮嶋正康,高橋久英,長尾枝澄香,飯島一誠,吉川徳茂
  • Organizer: 第47回日本小児腎臓病学会学術集会
  • Place of Presentation: 東京
• [Presentation] 繊毛病 (2012)
  • Author(s): 中西浩一
  • Organizer: 第47回日本小児腎臓病学会学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] ARPKDの病態・遺伝子診断 (2012)
  • Author(s): 中西浩一
  • Organizer: 第34回日本小児腎不全学会学術集会
  • Place of Presentation: 洲本（淡路島）
  • Invited
• [Presentation] Possible Contribution of Fibrocytes to Renal Fibrosis in Cpk Mouse, a Model of ARPKD (2012)
  • Author(s): Taketsugu Hama, Koichi Nakanishi, Hironobu Mukaiyama, Hiroko Togawa, Yuko Shima, Masayasu Miyajima, Hisahide Takahashi, Shizuko Nagao, Kazumoto Iijima, Norishige Yoshikawa
  • Organizer: 45th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego, USA
• [Presentation] 小児における多発性嚢胞腎PKDの会 (2011)
  • Author(s): 中西浩一
  • Organizer: 第11回関西座談会
  • Place of Presentation: 大阪(講演)
  • Year and Date: 2011-11-20
• [Presentation] cpkマウスにおける部位特定的リン酸化Smad3の発現 (2011)
  • Author(s): 浜武継,中西浩一,向山弘展,戸川寛子,島友子,宮嶋正康,高橋久英,長尾枝澄香,飯島一誠,吉川徳茂
  • Organizer: 第19回嚢胞性腎疾患研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-09-11
• [Presentation] Acceleration of Smad3 phosphorylation at linker regions via c-Jun NH2-terminal kinase (JNK) in cyst-lining epithelial cells in cpk mouse, a model of ARPKD (2011)
  • Author(s): Mukaiyama H, Nakanishi K, Hama T, Togawa H, Shima Y, Miyajima M, Takahashi H, Nagao S, Iijima K, Yoshikawa N
  • Organizer: 44^<th> Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia, USA(JASN 22:576A)
• [Presentation] cpkマウスARPKDモデルにおける上皮間葉移行(EMT) (2011)
  • Author(s): 向山弘展,中西浩一,戸川寛子,濵武継,島友子,宮嶋正康,吉原大輔,長尾枝澄香,高橋久英,飯島一誠,吉川徳茂
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] cpkマウスARPKDモデルにおける上皮間葉移行(EMT) (2011)
  • Author(s): 向山弘展,中西浩一,戸川寛子,濵武継,島友子,宮嶋正康,吉原大輔,長尾枝澄香,高橋久英,飯島一誠,吉川徳茂
  • Organizer: 第52回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Pathophysiology of polycystic kidney disease (2011)
  • Author(s): Nakanishi K
  • Organizer: The 11th Asian Congress of Pediatric Nephrology 2011(招待講演)
  • Place of Presentation: Fukuoka
• [Presentation] Acceleration of Smad3 phosphorylation at linker regions via c-Jun NH2-terminal kinase (JNK) in cyst-lining epithelial cells in cpk mouse, a model of ARPKD. (2011)
  • Author(s): Mukaiyama H, Nakanishi K, Hama T, Togawa H, Shima Y, Miyajima M, Takahashi H, Nagao S, Iijima K, Yoshikawa N
  • Organizer: The 44th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia
• [Presentation] cpkマウスにおける病的Smad3リン酸化
  • Author(s): 浜武継, 中西浩一, 向山弘展, 戸川寛子, 佐藤匡, 島 友子, 宮嶋正康, 野津寛大, 高橋久英, 長尾枝澄香, 飯島一誠, 吉川徳茂
  • Organizer: 第22回発達腎研究会
  • Place of Presentation: 高槻
• [Presentation] cpkマウスARPKDモデルにおける病的Smad3リン酸化
  • Author(s): 浜武継, 中西浩一, 向山弘展, 戸川寛子, 佐藤匡, 島 友子, 宮嶋正康, 野津寛大, 高橋久英, 長尾枝澄香, 飯島一誠, 吉川徳茂
  • Organizer: 第21回嚢胞性腎疾患研究会
  • Place of Presentation: 東京
• [Book] 遺伝性嚢胞性疾患.臨床腎臓内科学 (2013)
  • Author(s): 中西浩一,吉川徳茂(安田隆,平和伸仁,小山雄太編)
  • Publisher: 南山堂 東京
• [Book] 多発性嚢胞腎 14章 腎・尿細管機能異常 嚢胞性疾患 多発性嚢胞腎 「先天代謝異常ハンドブック」 (2013)
  • Author(s): 中西浩一,吉川徳茂(総編集 遠藤文夫 専門編集 山口清次,大浦敏博,奥山虎之)
  • Publisher: 中山書店 東京
• [Book] 遺伝性嚢胞性疾患. 臨床腎臓内科学 (2013)
  • Author(s): 中西浩一, 吉川徳茂
  • Publisher: 南山堂
• [Book] 多発性嚢胞腎(小児) 「腎疾患治療マニュアル2012-2013」 (2012)
  • Author(s): 中西浩一,吉川徳茂( 編集 「腎と透析」編集委員会)
  • Publisher: 東京医学社
• [Book] 第II部ARPKD(常染色体劣性多発性嚢胞腎) 多発性嚢胞腎診療ガイドQ&A (2011)
  • Author(s): 中西浩一(監修 松尾清一 編集 堀江重郎)
  • Publisher: 診断と治療社
• [Book] ARPKD（常染色体劣性多発性嚢胞腎） 多発性嚢胞腎診療ガイドQ&A (2011)
  • Author(s): 中西浩一 監修 松尾清一 編集 堀江重郎
  • Publisher: 診断と治療社