The development of the generative model for the renal tissue of ADPKD by juman iPS cell

• Project/Area Number: 15K10632
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Juntendo University
• Principal Investigator: HORIE SHIGEO 順天堂大学, 医学(系)研究科(研究院), 教授 (40190243)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 常染色体優性多発性嚢胞腎 / modifier gene / エクソンシークエンス / トルバプタン / 総腎容積 / ADPKD / iPS / 多発性嚢胞腎 / iPS細胞

Outline of Final Research Achievements

ADPKD (Autosomal Dominant Polycystic Kidney Disease) is a most frequent hereditary renal disease. Even within the same family, the age leading to end-stage renal failure is different. So it is believed that modifier genes other than disease genes influence disease progression. In this study, I performed exome sequencing on 100 cases and examined the influence of modifier 114 genes. In the mutation group of modifier genes, the increase rate of total kidney volume was significantly lower than that of the control group. So, the variation of modifier genes were considered to be a surrogate marker of tolvaptan efficacy.

Research Products

• [Journal Article] A cleavage product of Polycystin-1 is a mitochondrial matrix protein that affects mitochondria morphology and function when heterologously expressed. (2017)
  • Author(s): Lin CC, Kurashige M, Liu Y, Terabayashi T, Ishimoto Y, Wang T, Choudhary V, Hobbs R, Liu LK, Lee PH, Outeda P, Zhou F, Restifo NP, Watnick T, Kawano H, Horie S, Prinz W, Xu H, Menezes LF, Germino GG
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 1-19
  • DOI: 10.1038/s41598-018-20856-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Long-term safety profile of tolvaptan in autosomal dominant polycystic kidney disease patients: TEMPO Extension Japan Trial. (2017)
  • Author(s): Muto S, Okada T, Yasuda M, Tsubouchi H, Nakajima K, Horie S.
  • Journal Title: Drug Healthc Patient Saf Volume: 9 Pages: 93-104
  • DOI: 10.2147/dhps.s142825
  • Peer Reviewed / Open Access
• [Journal Article] Novel semi-automated kidney volume measurements in autosomal dominant polycystic kidney disease. (2017)
  • Author(s): Muto S, Kawano H, Isotani S, Ide H, Horie S.
  • Journal Title: Clin Exp Nephrol Volume: 印刷中 Issue: 3 Pages: 583-590
  • DOI: 10.1007/s10157-017-1486-6
  • Peer Reviewed / Open Access
• [Journal Article] Sensing the texture of imaging, a new biomarker of polycystic kidney disease. (2017)
  • Author(s): Horie S
  • Journal Title: Kidney Int Volume: 92 Issue: 5 Pages: 1044-5
  • DOI: 10.1016/j.kint.2017.05.031
  • Peer Reviewed / Open Access
• [Journal Article] Technical Evaluation: Identification of Pathogenic Mutations in PKD1 and PKD2 in Patients with Autosomal Dominant Polycystic Kidney Disease by Next-Generation Sequencing and Use of a Comprehensive New Classification System (2016)
  • Author(s): Kinoshita M, Higashihara E, Kawano H, Higashiyama R, Koga D, Fukui T, Gondo N, Oka T, Kawahara K, Rigo K, Hague T, Katsuragi K, Sudo K, Takeshi M, Horie S, Nutahara K.
  • Journal Title: PLos One Volume: 11 Issue: 11 Pages: e0166288-e0166288
  • DOI: 10.1371/journal.pone.0166288
  • Peer Reviewed
• [Journal Article] Evidence-based clinical practice guidelines for polycystic kidney disease 2014 (2016)
  • Author(s): Horie S, Mochizuki T, Muto S, Hanaoka K, Fukushima Y, Narita I, Nutahara K, Tsuchiya K, Tsuruya K, Kamura K, Nishio S, Suwabe T, Ubara Y, Ishimura E, Nakanishi K, Furukawa K, Kimura K, Matsuo S.
  • Journal Title: Clin Exp Nephrol Volume: 20 Issue: 4 Pages: 493-509
  • DOI: 10.1007/s10157-015-1219-7
  • Peer Reviewed
• [Presentation] Pharmacogenomics of Tolvaptan’s Inhibitory Effect on Kidney Volume Increase in Patients with Autosomal Dominant Polycystic Kidney Disease (2017)
  • Author(s): Horie S, Masuda M, Neuber S, Muto S, Okada T, Bergmann C
  • Organizer: American Society of Nephrology, Kidney Week 2017
  • Int'l Joint Research
• [Presentation] CKD stage3,4のADPKDに対するトルバプタン治療成績 (2016)
  • Author(s): 河野春奈，武藤 智，堀江重郎
  • Organizer: 第46回日本腎臓学会東部学術大会
  • Place of Presentation: 東京
  • Year and Date: 2016-10-07
• [Presentation] PKD外来新規開設１年半の受診動態と臨床統計 (2016)
  • Author(s): 河野春奈，武藤 智，堀江重郎
  • Organizer: 第104回日本泌尿器科学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-04-23