Gene expression profiling of glomerular component cells to understand molecular mechanisms of progression of chronic kidney diseases

• Project/Area Number: 25461220
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kyoto University
• Principal Investigator: Tsuchida Junichi 京都大学, 医学(系)研究科(研究院), 研究員 (10643570)
• Co-Investigator(Kenkyū-buntansha): MORI Kiyoshi 京都大学大学院医学研究科, メディカルイノベーションセンター, 特定准教授 (60343232)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 糸球体 / セルソーター / ポドサイト / 糖尿病性腎症 / 網羅的解析 / メサンギウム細胞 / 内皮細胞 / 細胞増殖 / 分泌蛋白 / 腎臓学 / ソーティング / 過剰発現

Outline of Final Research Achievements

Although approximately 65% of new patients entering dialysis in Japan are diabetic nephropathy and chronic glomerular nephritis, there are few therapeutic medication. To elucidate the mechanisms of progression of chronic kidney disease, ｗe generate transgenic mice expressing glomerular targeted fluorescent protein. We identified the secreted protein A, which is expressed specifically in podocytes, by gene expression profiling of the diabetic mice. Its expression was reduced in diabetic nephropathy, and it inhibited the proliferation of cultured mesangial cells.

Research Products

• [Journal Article] ENOS deficiency causes podocyte injury with mitochondrial abnormality. (2015)
  • Author(s): Ueda S, Ozawa S, Mori K, Asanuma K, Yanagita M, Uchida S, Nakagawa T.
  • Journal Title: Free Radic Biol Med Volume: 87 Pages: 181-192
  • Peer Reviewed
• [Journal Article] 循環器疾患における各種バイオマーカーの意義：TLR4と関連因子 (2015)
  • Author(s): 森潔、土田潤一、桒原孝成、横井秀基、笠原正登、向山政志、柳田素子
  • Journal Title: Heart View Volume: 19 Pages: 168-171
• [Presentation] Novel drug-inducible megalin knockout mice reveal marked increase of both total nephron glomerular filtration and tubular reabsorption of albumin in early diabetic nephropathy (2015)
  • Author(s): Keita P. Mori, Hideki Yokoi, Masato Kasahara, Takashige Kuwabara, Hirotaka Imamaki, Akira Ishii, Kazuwa Nakao, Tomomi Endo, Motoko Yanagita, Masashi Mukoyama, Kiyoshi Mori
  • Organizer: Annual Meeting of American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-11-05
  • Int'l Joint Research
• [Presentation] A Lack of eNOS Leads to Mitochondrial Injury in the Podocytes (2015)
  • Author(s): Shuko Ueda, Shota Ozawa, Kiyoshi Mori, Katsuhiko Asanuma, Motoko Yanagita, Shunya Uchida, Takahiko Nakagawa
  • Organizer: Annual Meeting of American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-11-05
  • Int'l Joint Research
• [Presentation] 高血圧・糖尿病による腎障害進展におけるポドサイトの重要性 (2015)
  • Author(s): 横井秀基、加藤有希子、大野祥子、森潔、中尾一和、柳田素子、向山政志
  • Organizer: 日本高血圧学会総会
  • Place of Presentation: 松山
  • Year and Date: 2015-10-09
• [Presentation] 薬剤誘導性遺伝子改変システムを用いた糖尿病性腎症におけるアルブミンの糸球体濾過量の評価 (2015)
  • Author(s): 森慶太、横井秀基、笠原正登、桒原孝成、今牧博貴、中尾一和、遠藤知美、柳田素子、向山政志、森潔
  • Organizer: 日本腎臓学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-06-05
• [Presentation] 慢性腎臓病における腎性貧血および線維化を担う神経堤由来線維芽細胞の機能解析 (2013)
  • Author(s): 中村仁、土田潤一、柳田素子ほか
  • Organizer: 日本腎臓学会学術総会
  • Place of Presentation: 東京
• [Remarks] 京都大学大学院医学研究科・メディカルイノベーションセンターTMKプロジェクト・森グループ研究内容
  • URL: http://www.tmk.med.kyoto-u.ac.jp/mori.html