Investigation of the novel therapeutic targets for diabetic nephropathy.

• Project/Area Number: 25461224
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Okayama University
• Principal Investigator: Shikata Kenichi 岡山大学, 大学病院, 教授 (00243452)
• Co-Investigator(Kenkyū-buntansha): Kodera Ryo 岡山大学, 大学病院・新医療研究開発センター, 助教 (70610921)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 糖尿病性腎症 / 炎症 / MicroRNA

Outline of Final Research Achievements

Chronic low grade inflammation, “microinflammation”, is one of the major mechanisms in the pathogenesis of diabetic nephropathy. The aim of this study is to clarify the role of microinflammation in the pathogenesis of diabetic nephropathy and find the novel therapeutic target for diabetic nephropathy. We investigated the change of expression of micro RNA in the glomeruli of the two types of mouse model using streptozotocin-induced type 1 diabetes and db/db mice. We performed Micro RNA array using RNA from diabetic mice and found several micro RNAs which up-regulated in the glomeruli of both diabetic mouse models. Moreover, these microRNA upregulated in the glomeruli for long period from the early phase of diabetes. One of these microRNA induced up-regulation of TGF-beta and down-regulaton of eNOS and SIRT-1 after transfection in glomerular endothelial cells and mesangial cells. These results suggest that micro RNA might be one of the new therapeutic target for diabetic nephropathy.

Research Products

• [Journal Article] Factors associated with remission and/or regression of microalbuminuria in type 2 diabetes mellitus. (2014)
  • Author(s): Ono T, Shikata K, Obika M, Miyatake N, Kodera R, Hirota D, Wada J, Kataoka H, Ogawa D, Makino H
  • Journal Title: Acta Medica Okayama Volume: 68 Pages: 235-241
  • NAID: 120005465586
  • Peer Reviewed
• [Journal Article] Lifestyle modification is associated with improving estimated glomerular filtration rate (eGFR) and proteinuria in Japanese with proteinuria. (2014)
  • Author(s): Miyatake N, Shikata K, Makino H, Numata T
  • Journal Title: Acta Med Okayama Volume: 68 Pages: 43-46
  • NAID: 120005372645
  • Peer Reviewed
• [Presentation] わが国の臨床研究から何を学べば良いか：DNETT-Japan (2016)
  • Author(s): 四方賢一
  • Organizer: 第50回糖尿病学の進歩 シンポジウム
  • Place of Presentation: 東京都
  • Year and Date: 2016-02-10
  • Invited
• [Presentation] 腎症の成因と新たな治療標的 (2015)
  • Author(s): 四方賢一
  • Organizer: 第30回日本糖尿病合併症学会、第21回日本糖尿病眼学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-11-27
  • Invited
• [Presentation] 糖尿病性腎症診療の現状と課題 (2015)
  • Author(s): 四方賢一
  • Organizer: 第45回日本腎臓学会西部学術集会ワークショップ
  • Place of Presentation: 金沢市
  • Year and Date: 2015-10-24
  • Invited
• [Presentation] 糖尿病腎症の診断と治療 (2015)
  • Author(s): 四方賢一
  • Organizer: 日本内科学会北陸支部第66回生涯教育講演会
  • Place of Presentation: 金沢市
  • Year and Date: 2015-09-06
  • Invited
• [Presentation] 腎症治療薬開発の現状と課題、 (2015)
  • Author(s): 四方賢一
  • Organizer: 第58回日本糖尿病学会年次学術集会 シンポジウム
  • Place of Presentation: 下関市
  • Year and Date: 2015-05-23
  • Invited
• [Presentation] 腎症に対する薬物療法 (2014)
  • Author(s): 四方賢一
  • Organizer: 第29回日本糖尿病合併症学会シンポジウム3
  • Place of Presentation: 東京都
  • Year and Date: 2014-10-03
  • Invited
• [Presentation] 糖尿病性腎症と炎症～新規治療薬開発への道～ (2014)
  • Author(s): 四方賢一
  • Organizer: 第57回日本腎臓学会学術総会 教育セッション2 糖尿病腎症
  • Place of Presentation: 横浜市
  • Year and Date: 2014-07-05
  • Invited
• [Presentation] インクレチン関連薬の長期展望
  • Author(s): 四方賢一
  • Organizer: 第56回日本糖尿病年次学術集会
  • Place of Presentation: 熊本市
• [Presentation] 糖尿病性腎症の診断と治療
  • Author(s): 四方賢一
  • Organizer: 第48回糖尿病学の進歩
  • Place of Presentation: 札幌市
  • Invited