Investigation of therapeutic effect of vitamin A on ciliopathy and promotion of its therapeutic effect

• Project/Area Number: 15K16222
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits
• Research Institution: Fujita Health University
• Principal Investigator: KUGITA Masanori 藤田保健衛生大学, 疾患モデル教育研究施設, 講師 (50440681)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 繊毛病 / RXR / ビタミンA / ビタミンK / 多発性嚢胞腎症 / ネフロン癆

Outline of Final Research Achievements

Nephronophthisis (NPH) and polycystic kidney disease (PKD) stemmed from abnormal function of cilia-related proteins which are coaded by the gene including mutation. Therefore they are called ciliopathy. We found that retinoid X receptor (RXR) could relate to cystogenesis is a character of ciliopathy. A ligand of RXR is 9-cis retinoic acid (9cRA) of vitamin A metabolite. Therefore we investigated that the suppression effect of vitamin A on ciliopathy using cells and model animals for ciliopathy.
We show that the narrow range of optimal concentration of 9cRA which has effect only on ciliopathy, and ingestion of a large amount of vitamin A could worsen pathological condition of ciliopathy.

Research Products

• [Presentation] Increased salt intakes dose not deteriorate renal cystic disease progression in high water loaded PCK rats. (2016)
  • Author(s): Masanori Kugita, Tamio Yamaguchi, Yoichi Nagamura, Harold M Aukema, Shizuko Nagao
  • Organizer: Kidney Week 2016
  • Place of Presentation: Chicago, IL, U.S.A.
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] 多発性嚢胞腎症モデル動物の腎臓におけるRXRの発現と局在 (2016)
  • Author(s): 吉原大輔、釘田雅則、長尾静子
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2016-06-17
• [Presentation] 多発性嚢胞腎症モデル動物の腎臓におけるRXRの発現と局在 (2016)
  • Author(s): 吉原大輔、釘田雅則、長尾静子
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-06-17
• [Presentation] 多発性嚢胞腎症モデル動物の腎臓におけるレチノイドX受容体の解析 (2016)
  • Author(s): 釘田雅則、吉原大輔、加藤由布、小木曽昇、下村恭代、西田修、長尾静子
  • Organizer: 第63回日本実験動物学会総会
  • Place of Presentation: 川崎、ミューザ川崎シンフォニー
  • Year and Date: 2016-05-18
• [Presentation] 多発性嚢胞腎症モデル動物の腎臓におけるレチノイドX受容体の解析 (2016)
  • Author(s): 釘田雅則、吉原大輔、加藤由布、小木曽 昇、下村恭代、西田修、長尾静子
  • Organizer: 第63回日本実験動物学会総会
  • Place of Presentation: 川崎
  • Year and Date: 2016-05-18
• [Presentation] 嚢胞性腎疾患モデル動物における有用性の比較 (2015)
  • Author(s): 釘田雅則、吉原大輔、田代遥、加藤雅也、長尾静子
  • Organizer: 第87回東海実験動物研究会
  • Place of Presentation: 岐阜
  • Year and Date: 2015-12-12
• [Presentation] Retinoid X receptor pathway, a novel signaling cascade responsible for cystogenesis in three rodent models of polycystic kidney disease. (2015)
  • Author(s): Yoshihara D, Kugita M, Aukema HM, Yamaguchi T, Nagao S.
  • Organizer: American Society of Nephrology Kidney Week 2015
  • Place of Presentation: San Diego, CA, U.S.A.
  • Year and Date: 2015-11-03
• [Presentation] 核内受容体を介した情報伝達経路の解析 (2015)
  • Author(s): 釘田雅則、吉原大輔、長尾静子
  • Organizer: 第1回シーズ・ニーズ発表交流会
  • Place of Presentation: 豊明
  • Year and Date: 2015-07-23
• [Presentation] Expression and distribution of retinoid X receptor in rodent models of polycystic kidney disease. (2015)
  • Author(s): Yoshihara D, Kugita M, Sasaki M, Nagao S.
  • Organizer: 11th ASPR Congress & the 118th Annual Meeting of the Japan Pediatric Society
  • Place of Presentation: Osaka
  • Year and Date: 2015-04-15
• [Remarks] 藤田保健衛生大学疾患モデル科学業績
  • URL: http://www.fujita-hu.ac.jp/CAMHD/LAS/achievement/achievement.html
• [Remarks] 藤田保健衛生大学疾患モデル科学研究
  • URL: http://www.fujita-hu.ac.jp/CAMHD/LAS/research/research.html