Novel mechanism of progression of diabetic nephropathy by hyperlipidemia: MRP8/TLR4 signaling

• Project/Area Number: 23790939
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Kyoto University
• Principal Investigator: KUWABARA Takashige 京都大学, 大学院・医学研究科, 医員 (00393356)
• Co-Investigator(Kenkyū-buntansha): MORI Kiyoshi 京都大学, 大学院・医学研究科, 准教授 (60343232)
• Research Collaborator: NISHIYAMA Akira 香川大学, 医学部, 教授 (10325334)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 糖尿病性腎症 / 自然炎症 / TLR4 / MRP8 / マクロファージ / 脂質代謝異常

Research Abstract

Homeostatic inflammation which is induced by endogenous ligands and pathogenic receptors has been emerged as a molecular basis of life style-related diseases. In this study, it has been clarified that MRP8/TLR4 signaling, involved in homeostatic inflammation, might play an important role in the progression of diabetic nephropathy. Furthermore, renal MRP8 expression in human biopsy samples could predict the renal prognosis of diabetic nephropathy. Blockade of MRP8/TLR4 signaling could become a novel strategy for diabetic nephropathy.

Research Products

• [Journal Article] Peritoneal fibrosis and high transport are induced in mildly pre-injured peritoneum by 3,4-dideoxyglucosone-3-ene in mice (2013)
  • Author(s): Yokoi, H., Kasahara, M., Mori, K., Kuwabara, T., Toda, N., Yamada, R., Namoto, S., Yamamoto, T., Seki, N., Souma, N., Yamaguchi, T., Sugawara, A., Mukoyama, M., Nakao, K.
  • Journal Title: Peritoneal Dialysis International Volume: 33(2) Issue: 2 Pages: 143-154
  • DOI: 10.3747/pdi.2011.00033
  • Peer Reviewed
• [Journal Article] Peritoneal Fibrosis and High Transport Are Induced in Mildly Pre-injured Peritoneum by 3,4-Dideoxyglucosone-3-ene in Mice. (2013)
  • Author(s): Hideki Yokoi
  • Journal Title: Perit Dial Int Volume: 33 Pages: 143-154
  • Peer Reviewed
• [Journal Article] Natriuretic peptide receptor guanylyl cyclase-A protects podocytes from aldosterone-induced glomerular injury. (2013)
  • Author(s): Yoshihisa Ogawa
  • Journal Title: J Am Soc Nephrol Volume: 23 Pages: 1198-1209
  • Peer Reviewed
• [Journal Article] Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice (2012)
  • Author(s): Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Saito Y, Ogawa Y, Imamaki H, Kawanishi T, Ishii A, Koga K, Mori KP, Kato Y, Sugawara A, Nakao K
  • Journal Title: Diabetologia Volume: 55:2256-2266 Issue: 8 Pages: 2256-2266
  • DOI: 10.1007/s00125-012-2578-1
  • NAID: 120004225542
  • Peer Reviewed
• [Journal Article] Natriuretic peptide receptor guanylyl cyclase-A protects podocytes from aldosterone-induced glomerular injury (2012)
  • Author(s): Ogawa Y, Mukoyama M, Yokoi H, Kasahara M, Mori K, Kato Y, Kuwabara T, Imamaki H, Kawanishi T, Koga K, Ishii A, Tokudome T, Kishimoto I, Sugawara A, Nakao K
  • Journal Title: J Am Soc Nephrol Volume: 23:1198-1209 Issue: 7 Pages: 1198-1209
  • DOI: 10.1681/asn.2011100985
  • Peer Reviewed
• [Journal Article] Pleiotrophin triggers inflammation and increased peritoneal permeability leading to peritoneal fibrosis (2012)
  • Author(s): Yokoi H, Nakao K, et al
  • Journal Title: Kidney Int. Volume: 81 Issue: 2 Pages: 160-169
  • DOI: 10.1038/ki.2011.305
  • Peer Reviewed
• [Journal Article] Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by toll-like receptor 4 in mice (2012)
  • Author(s): Takashige Kuwabara
  • Journal Title: Diabetologia Volume: 55 Pages: 2256-2266
  • Peer Reviewed
• [Journal Article] Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by toll-like receptor 4 in mice (2012)
  • Author(s): T Kuwabara, K Mori, M Mukoyama, et al.
  • Journal Title: Diabetologia Volume: in press
  • NAID: 120004225542
  • Peer Reviewed
• [Journal Article] Natriuretic peptide receptor guanylyl cyclase-A protects podocytes from aldosterone-induced glomerular injury. (2012)
  • Author(s): Y Ogawa, M Mukoyama, T Kuwabara, et al.
  • Journal Title: J Am Soc Nephrol Volume: in press
  • Peer Reviewed
• [Journal Article] 糖尿病性腎症と脂質代謝異常 (2012)
  • Author(s): 桑原孝成、向山政志、中尾一和
  • Journal Title: Annual Review腎臓2012 Volume: 1 Pages: 133-139
• [Presentation] 糖尿病性腎症の治療薬を目指して「糖尿病性腎症における自然炎症の役割～MRP8/TLR4シグナル経路～」 (2012)
  • Author(s): 桑原孝成
  • Organizer: 協和発酵キリン腎臓シンポジウム
  • Year and Date: 2012-11-23
• [Presentation] Macrophage-mediated glucolipotoxicity contributes to progression of diabetic nephropathy through MRP8/TLR4 signaling (2012)
  • Author(s): Kuwabara T
  • Organizer: Annual Meeting of American Society of Nephrology.
  • Place of Presentation: San Diego, USA
  • Year and Date: 2012-11-02
• [Presentation] 若手シンポジウム「炎症メディエーターMRP8/TLR4 が糖尿病性腎症進展に果たす役割とは (2012)
  • Author(s): 桑原孝成
  • Organizer: FRONT-J 第3回学術集会
  • Year and Date: 2012-08-11
• [Presentation] ワークショップ 3 糖尿病性腎症の新たな発症、進行メカニズム「自然免疫受容体 TLR4 が糖尿病性腎症進展に果たす役割-脂質による悪化-」 (2012)
  • Author(s): 桑原孝成
  • Organizer: 第55回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2012-06-02
• [Presentation] Macrophage-mediated glucolipotoxicity contributes to progression of diabetic nephropathy through MRP8/TLR4 signaling (2012)
  • Author(s): Takashige Kuwabara
  • Organizer: Annual Meeting of American Society of Nephrology
  • Place of Presentation: San Diego, USA
• [Presentation] ワークショップ3 糖尿病性腎症の新たな発症、進行メカニズム「自然免疫受容体TLR4が糖尿病性腎症進展に果たす役割-脂質による悪化-」 (2012)
  • Author(s): 桑原孝成
  • Organizer: 第55回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 若手シンポジウム「炎症メディエーターMRP8/TLR4が糖尿病性腎症進展に果たす役割とは」 (2012)
  • Author(s): 桑原孝成
  • Organizer: FRONT-J 第3回学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Toll-Like Recepotor 4-Mediated, Hyperinsulinemia-Independent Progression of Diabetic Nephropathy by Hyperlipidemia. (2011)
  • Author(s): T Kuwabara, K Mori, M Mukoyama, et al.
  • Organizer: Annual Meeting of American Diabetes Association
  • Place of Presentation: San Diego Convension Center, US
• [Presentation] Aggravation of diabetic nephropathy by hyperlipidemia is mediated by MRP8/TLR4 signaling in macrophages. (2011)
  • Author(s): T Kuwabara, K Mori, M Mukoyama, et al.
  • Organizer: Annual Meeting of American Society of Nephrology
  • Place of Presentation: Philadelphia Convension Center, US
• [Book] 糖尿病性腎症における自然炎症の意義とその分子機序 (2013)
  • Author(s): 桑原孝成
  • Total Pages: 7
  • Publisher: フジメディカル出版
• [Book] Annual Review 腎臓 (2012)
  • Author(s): 桑原孝成、向山政志、中尾一和.
  • Publisher: 中外医学社
• [Book] ナトリウム利尿ペプチド (2012)
  • Author(s): 桑原孝成
  • Total Pages: 7
  • Publisher: ライフメディコム
• [Remarks] 京都大学大学院医学研究科内分泌代謝内科
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/index-jp.html
• [Remarks] 京都大学内分泌代謝内科
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/index-jp.html