Development of novel treatment for diabetic nephropathy originate from functional modified peptides of pigment epitherium-derived factor.

• Project/Area Number: 16K07101
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Kurume University
• Principal Investigator: Matsui Takanori 久留米大学, 医学部, 講師 (10425233)
• Co-Investigator(Kenkyū-buntansha): 東元 祐一郎 久留米大学, 医学部, 教授 (40352124)
• Research Collaborator: Yamagishi Shoichi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 糖尿病腎症 / 機能性ペプチド / PEDF / PEDFペプチド / 疾患モデル / 修飾ペプチド

Outline of Final Research Achievements

We examined a recombinant fragment of PEDF could inhibit reactive oxigen species generation and gene expression of MCP-1, ICAM-1, PAI-1 in AGEs-exposed renal mesangial cells. A PEDF-derived sythetic peptide exert anti-oxidative stress and inflammatory actions.

Academic Significance and Societal Importance of the Research Achievements

糖尿病腎症は新規透析導入の原因疾患第一位であり、毎年1万6千人が透析導入に至っており、社会問題となっている。
今回得られたペプチドは、PEDFと同様に抗酸化ストレス、抗炎症作用を発揮した。このペプチドはAGE-RAGE系を抑えることで糖尿病腎症、動脈硬化症や糖尿病網膜症に対しても保護的に作用する可能性が見出された。PEDFは不安定なタンパク質であり、大量精製には費用も高額になるが、同等の機能を発揮するペプチドを用いることで、新規の糖尿病腎症治療法の開発に繋がることが期待される。

Research Products

• [Journal Article] Pathological role of advanced glycation end products (AGEs) and their receptor axis in atrial fibrillation (2019)
  • Author(s): Yamagishi Sho-ichi、Sotokawauchi Ami、Matsui Takanori
  • Journal Title: Mini-Reviews in Medicinal Chemistry Volume: 19 Issue: 13 Pages: 1040-1048
  • DOI: 10.2174/1389557519666190311140737
  • Peer Reviewed
• [Journal Article] Serum Levels of Protein-Bound Methylglyoxal-Derived Hydroimidazolone-1 are Independently Correlated with Asymmetric Dimethylarginine (2019)
  • Author(s): Tahara Nobuhiro、Kojima Ruchia、Yoshida Risa、Bekki Munehisa、Sugiyama Yoichi、Tahara Atsuko、Maeda Shoko、Honda Akihiro、Igata Sachiyo、Nakamura Tomohisa、Sun Jiahui、Matsui Takanori、Fukumoto Yoshihiro、Matsui Toshiro、Yamagishi Sho-Ichi
  • Journal Title: Rejuvenation Research Volume: 印刷中 Issue: 5 Pages: 431-438
  • DOI: 10.1089/rej.2018.2152
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Switching dipeptidyl peptidase-4 inhibitors to tofogliflozin, a selective inhibitor of sodium-glucose cotransporter 2 improves arterial stiffness evaluated by cardio-ankle vascular index in patients with type 2 diabetes (2019)
  • Author(s): Tahara Nobuhiro、Yamagish Sho-ichi、Bekki Munehisa、Tahara Atsuko、Igata Sachiyo、Honda Akihiro、Sugiyama Yoichi、Nakamura Tomohisa、Sun Jiahui、Kumashiro Yuki、Matsui Takanori、Fukumoto Yoshihiro
  • Journal Title: Current Vascular Pharmacology Volume: 17 Issue: 4 Pages: 411-420
  • DOI: 10.2174/1570161116666180515154555
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Role of Hyperglycemia-Induced Advanced Glycation End Product (AGE) Accumulation in Atherosclerosis (2018)
  • Author(s): Yamagishi Sho-ichi、Matsui Takanori
  • Journal Title: Annals of Vascular Diseases Volume: 11 Issue: 3 Pages: 253-258
  • DOI: 10.3400/avd.ra.18-00070
  • NAID: 130007487741
  • ISSN: 1881-641X, 1881-6428
  • Year and Date: 2018-09-25
  • Peer Reviewed
• [Journal Article] Advanced glycation end products evoke inflammatory reactions in proximal tubular cells via autocrine production of dipeptidyl peptidase-4 (2018)
  • Author(s): Kaifu Kumiko、Ueda Seiji、Nakamura Nobutaka、Matsui Takanori、Yamada-Obara Nana、Ando Ryotaro、Kaida Yusuke、Nakata Masami、Matsukuma-Toyonaga Maki、Higashimoto Yuichiro、Fukami Kei、Suzuki Yusuke、Okuda Seiya、Yamagishi Sho-ichi
  • Journal Title: Microvascular Research Volume: 120 Pages: 90-93
  • DOI: 10.1016/j.mvr.2018.07.004
  • Peer Reviewed / Open Access
• [Journal Article] Role of Ligands of Receptor for Advanced Glycation End Products (RAGE) in Peripheral Artery Disease (2018)
  • Author(s): Yamagishi Sho-ichi、Matsui Takanori
  • Journal Title: Rejuvenation Research Volume: 21 Issue: 5 Pages: 456-463
  • DOI: 10.1089/rej.2017.2025
  • Peer Reviewed
• [Presentation] 終末糖化産物受容体(RAGE)アプタマーは動物モデルの糖尿病腎症の発症・増悪,悪性黒色腫の増殖・転移を抑制する (2018)
  • Author(s): 松井孝憲, 中村信孝, 東元祐一郎, 山岸昌一
  • Organizer: 日本核酸医薬学会第4回年会
• [Presentation] 終末糖化産物受容体(RAGE)アプタマーはラットの糖尿病腎症の発症と進展を抑制する (2018)
  • Author(s): 松井孝憲, 山岸昌一
  • Organizer: 第61回日本腎臓学会
• [Presentation] 児玉豪, 伊藤佐久耶, 甲斐田裕介, 甲斐友宝, 松井孝憲, 山岸昌一, 深水圭 (2018)
  • Author(s): カナグリフロジンはヒト近位尿細管細胞におけるCarboxymethyl Lysine産生を抑制する
  • Organizer: 第61回日本腎臓学会
• [Presentation] トホグリフロジンは尿細管保護効果により2型糖尿病マウスの腎障害を改善する (2018)
  • Author(s): 松井 孝憲、石橋裕二、山岸 昌一
  • Organizer: 第61回日本糖尿病学会
• [Presentation] 外川内亜美、中村信孝、松井 孝憲、山岸 昌一 (2018)
  • Author(s): 終末糖化産物受容体（RAGE）阻害アプタマーは、ヌードマウスにおいて悪性メラノーマの増殖と転移を抑える
  • Organizer: 第61回日本糖尿病学会
• [Presentation] 終末糖化産物受容体(RAGE)のアプタマーは動物の糖尿病腎症の発症・増悪と悪性黒色腫の増殖・転移を阻害する (2018)
  • Author(s): 松井孝憲，中村信孝, 東元祐一郎, 山岸昌一
  • Organizer: 第41回日本分子生物学会