Gene analysis of renal coloboma syndrome and biomarker development of acute kidney injury

• Project/Area Number: 26293126
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Kanazawa University
• Principal Investigator: FURUICHI KENGO 金沢大学, 大学病院, 准教授 (50432125)
• Co-Investigator(Kenkyū-buntansha): 和田 隆志 金沢大学, 医学系, 教授 (40334784) ; 岩田 恭宜 金沢大学, 大学病院, 助教 (90432137) ; 長船 健二 京都大学, 学内共同利用施設等, 教授 (80502947)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000); Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
• Keywords: 腎コロボーマ症候群 / 急性腎障害 / PAX2 / KIF26B / 稀少遺伝性疾患 / 線維化 / 炎症 / 腎虚血再還流障害 / 造影剤腎症

Outline of Final Research Achievements

In this study, gene analysis of renal coloboma syndrome, which is a rare genetic disease, and biomarker development of acute kidney injury, were evaluated from the viewpoint of PAX2 gene. In this study, four genes other than PAX2 were identified from cases of renal coloboma syndrome. Among them, we reported a case of human KIF 26 B gene mutation, which is the world's first report. In addition, in the study of acute kidney injury by animal models and cultured cell experiments, the roles of the Pax2 gene in pathogenesis of kidney disease and molecular mechanisms were revealed. Moreover, candidates of new biomarkers were discovered. In addition, the possibility of a new biomarker molecule was also evaluated in the study of human acute kidney injury.

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 Int. 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
• [Journal Article] Messenger RNA expression profile of sleep-related genes in peripheral blood cells in patients with chronic kidney disease. (2015)
  • Author(s): Kitajima S, Iwata Y, Furuichi K, Sagara A, Shinozaki Y, Toyama T, Sakai N, Shimizu M, Sakurai T, Kaneko S, Wada T.
  • Journal Title: Clin Exp Nephrol Volume: 20 Issue: 2 Pages: 218-25
  • DOI: 10.1007/s10157-015-1150-y
  • Peer Reviewed / Open Access
• [Journal Article] Revisiting inflammation in diabetic nephropathy: the role of the Nlrp3 inflammasome in glomerular resident cells (2015)
  • Author(s): Sakai N, Wada T
  • Journal Title: Kidney Int Volume: 87 Pages: 12-14
  • Peer Reviewed
• [Journal Article] Pro-inflammatory/Th1 gene expression shift in high glucose stimulated mesangial cells and tubular epithelial cells. (2014)
  • Author(s): Iwata Y, Furuichi K, Hashimoto S, Yokota K, Yasuda H, Sakai N, Kitajima S, Toyama T, Shinozaki Y, Sagara A, Matsushima K, Kaneko S, Wada T.
  • Journal Title: Biochem Biophys Res Commun Volume: 443 Issue: 3 Pages: 969-974
  • DOI: 10.1016/j.bbrc.2013.12.072
  • Peer Reviewed / Open Access
• [Journal Article] Impact of kidney function and urinary protein excretion on pulmonary function in Japanese patients with chronic kidney disease. (2014)
  • Author(s): Nakade Y, Toyama T, Furuichi K, Kitajima S, Ohkura N, Sagara A, Shinozaki Y, Hara A, Kitagawa K, Shimizu M, Iwata Y, Oe H, Nagahara M, Horita H, Sakai Y, Kaneko S, Wada T.
  • Journal Title: Clin Exp Nephrol Volume: - Issue: 5 Pages: 763-9
  • DOI: 10.1007/s10157-013-0920-7
  • Peer Reviewed
• [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] 糖尿病性腎症のコホート研究とバイオマーカー (2016)
  • Author(s): 古市賢吾・和田隆志
  • Organizer: 第46回日本腎臓学会西部学術大会
  • Place of Presentation: 宮崎
  • Year and Date: 2016-10-14
• [Presentation] 虚血性腎疾患 (2016)
  • Author(s): 古市賢吾・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: 2016-06-19
• [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] Kidney Biopsy Study of Diabetic nephropathy in Japan (2015)
  • Author(s): Kengo Furuichi, Takashi Wada
  • Organizer: International Symposium on “CKD Cohort Study In Asia 2015”
  • Place of Presentation: ソウル(韓国）
  • Year and Date: 2015-11-28
  • Int'l Joint Research / Invited
• [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] 次世代シーケンサーが導くバイオマーカーの開拓 (2014)
  • Author(s): 岩田恭宜、和田隆志
  • Organizer: 日本臨床検査自動化学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-10-09 – 2014-10-11
  • Invited
• [Presentation] 腎コロボーマ症候群の遺伝子診断と臨床的特徴 (2014)
  • Author(s): 2.奥村利矢・相良明宏・篠崎康之・北島信治・遠山直志・岩田恭宜・坂井宣彦・清水美保・古市賢吾・和田隆志・東出朋巳・杉山和久
  • Organizer: 日本腎臓学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] 培養メサンギウム細胞と尿細管細胞における高糖刺激下での炎症関連遺伝子発現の解析 (2014)
  • Author(s): 岩田恭宜、橋本真一、古市賢吾、和田隆志
  • Organizer: 日本炎症・再生医学会
  • Place of Presentation: 沖縄
  • Year and Date: 2014-07-01 – 2014-07-04