Pathophysiological analysis using iPS cells from patient with Renal Coloboma syndrome

• Project/Area Number: 15K15328
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Kanazawa University
• Principal Investigator: FURUICHI KENGO 金沢大学, 附属病院, 准教授 (50432125)
• Co-Investigator(Kenkyū-buntansha): 和田 隆志 金沢大学, 医学系, 教授 (40334784) ; 長船 健二 京都大学, iPS細胞研究所, 教授 (80502947)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ＰＡＸ2 / 腎コロボーマ症候群 / 疾患特異iPS細胞 / PAX2 / 経時的発現遺伝子解析 / 疾患特異的iPS細胞 / 再生 / 修復

Outline of Final Research Achievements

In this study, we established disease-specific iPS cells from renal coloboma syndrome with PAX2 gene mutation, which is a rare genetic disorder. To clarify the pathogenesis of this syndrome, we used these iPS cells. The cells were also used to investigate therapeutic target genes.
We induced kidney lineage cells, such as mesoderm and renal tubules, from disease-specific and control iPS cells. In addition, time-sequential expression gene analysis was performed. Some gene expressions were enhanced in response to gene expression of PAX2, and some candidate genes in which expression was reduced in disease specific iPS cells was detected.

Research Products

• [Journal Article] Nationwide multicentre kidney biopsy study of Japanese patients with type 2 diabetes. (2017)
  • Author(s): Furuichi K, Yuzawa Y, Shimizu M, Hara A, Toyama T, Kitamura H, Suzuki Y, Sato H, Uesugi N, Ubara Y, Hisano S, Ueda Y, Nishi S, Yokoyama H, Nishino T, Kohagura K, Ogawa D, Mise K, Shibagaki Y, Kimura K, Haneda M, Makino H, Matsuo S, Wada T.
  • Journal Title: Nephrol Dial Transplant Volume: 印刷中 Issue: 1 Pages: 138-148
  • DOI: 10.1093/ndt/gfw417
  • NAID: 120006460355
  • Peer Reviewed / Open Access
• [Journal Article] Impairment of the carnitine/organic cation transporter 1-ergothioneine axis, an adaptive antioxidant system, is mediated by intestinal transporter dysfunction in chronic kidney disease (2017)
  • Author(s): Yasuyuki Shinozaki, Kengo Furuichi, Tadashi Toyama, Shinji Kitajima, Akinori Hara, Yasunori Iwata, Norihiko Sakai, Miho Shimizu, Shuichi Kaneko, Noriyoshi Isozumi, Shushi Nagamori, Yoshikatsu Kanai, Tomoko Sugiura, Yukio Kato, Takashi Wada
  • Journal Title: Kidney international Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clinical significance of urinary liver-type fatty acid-binding protein as a predictor of ESRD and CVD in patients with CKD. (2016)
  • Author(s): Matsui K, Kamijo-Ikemori A, Imai N, Sugaya T, Yasuda T, Tatsunami S, Toyama T, Shimizu M, Furuichi K, Wada T, Shibagaki Y, Kimura K.
  • Journal Title: Clin Exp Nephrol Volume: 20 Issue: 2 Pages: 195-203
  • DOI: 10.1007/s10157-015-1144-9
  • Peer Reviewed
• [Journal Article] Association of PAX2 and Other Gene Mutations with the Clinical Manifestations of Renal Coloboma Syndrome. (2015)
  • Author(s): Okumura T, Furuichi K, Higashide T, Sakurai M, Hashimoto S, Shinozaki Y, Hara A, Iwata Y, Sakai N, Sugiyama K, Kaneko S, Wada T.
  • Journal Title: PLoS One Volume: 10 Issue: 11 Pages: e0142843-e0142843
  • DOI: 10.1371/journal.pone.0142843
  • Peer Reviewed / Open Access
• [Presentation] Chronic inflammation and fibrosis in kidney diseases. (2017)
  • Author(s): Takashi Wada
  • Organizer: The 19th Takeda Science Foundation Symposium on Bioscience
  • Place of Presentation: 東京
  • Year and Date: 2017-01-21
  • Int'l Joint Research / Invited
• [Presentation] Nationwide Multicenter Kidney Biopsy Study of Japanese Patients with Type 2 Diabetes (2016)
  • Author(s): Kengo Furuichi, Yukio Yuzawa, Yoshifumi Ubara, Miho Shimizu, Tadashi Toyama, Yasunori Iwata, Norihiko Sakai, Takashi Wada
  • Organizer: ASN Kidney Week 2016
  • Place of Presentation: シカゴ（アメリカ）
  • Year and Date: 2016-11-19
  • Int'l Joint Research
• [Presentation] Apoptosis Inhibitor of Macrophage (AIM) Expression in the Kidney Was Associated with Increased Proteinuria and Decline in Renal Function. (2016)
  • Author(s): Yasunori Iwata, Megumi Oshima, Kengo Furuichi, Norihiko Sakai, Miho Shimizu, Akinori Hara, Tadashi Toyama, Yasuyuki Shinozaki, Yasutaka Kamikawa, Shinji Kitajima, Akihiro Sagara, Takashi Wada
  • Organizer: ASN Kidney Week 2016
  • Place of Presentation: シカゴ（アメリカ）
  • Year and Date: 2016-11-19
  • Int'l Joint Research
• [Presentation] Ergothioneine Plays a Key Role in Kidney-Intestinal Interaction of CKD through Organic Cation Transporter 1 Dysfunction. (2016)
  • Author(s): Yasuyuki Shinozaki, Kengo Furuichi, Shinji Kitajima, Tadashi Toyama, Akinori Hara, Yasunori Iwata, Norihiko Sakai, Miho Shimizu, Takashi Wada
  • Organizer: ASN Kidney Week 2016
  • Place of Presentation: シカゴ（アメリカ）
  • Year and Date: 2016-11-18
  • Int'l Joint Research
• [Presentation] 腎硬化症の臨床病理学的検討 (2016)
  • Author(s): 古市賢吾・遠山直志・原章規・清水美保・北村博司・鈴木芳樹・佐藤博・湯澤由紀夫・和田隆志
  • 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] 腎障害進展因子としてのPAX2の意義 (2016)
  • Author(s): 古市賢吾・奥村利矢・牧石祥平・迫恵輔・山村雄太 原章規・岩田恭宜・坂井宣彦・清水美保・和田隆志
  • Organizer: 第61回日本透析医学会学術集会・総会
  • Place of Presentation: 大阪
  • Year and Date: 2016-06-10
• [Presentation] Association of PAX2 and Other Gene Mutations with the Clinical Manifestations of Renal Coloboma Syndrome (2015)
  • Author(s): Kengo Furuichi, Toshiya Okumura, Shin-ichi Hashimoto, Yasuyuki Shinozaki, Yasunori Iwata, Norihiko Sakai, Takashi Wada
  • Organizer: ASN(米国腎臓学会）
  • Place of Presentation: サンディエゴ（USA)
  • Year and Date: 2015-11-06
  • Int'l Joint Research
• [Presentation] 本邦における糖尿病性腎症研究：臨床、病理、バイオマーカーの接点と展開 (2015)
  • Author(s): 古市賢吾、和田隆志
  • Organizer: 日本腎臓学会西部学術大会
  • Place of Presentation: 金沢（金沢歌劇座）
  • Year and Date: 2015-10-24