Investigation of mechanisms and regulatory pathways of p27kip expression in macrophages and the role of p27kip in the pathogenesis of atherosclerosis

• Project/Area Number: 15K19519
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Kumamoto University
• Principal Investigator: Ishii Norio 熊本大学, 医学部附属病院, 特任助教 (10599111)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 動脈硬化 / 脂質代謝異常 / マクロファージ / 細胞周期

Outline of Final Research Achievements

As for the pathophysiological significance of the macrophage proliferation in the atherosclerosis, there are still many questions left to be answered. To verify the direct evidence of involvement of local macrophage proliferation for atherosclerosis, we generated transgenic mice received p27kip expression only in the macrophages(mac-p27Tg), whose macrophage proliferation was specifically inhibited. The aortic valve annulus section average plaque area was significantly reduced in mac-p27Tg, compared with that of the control. The percentage of the necrotic core to the total advanced lesion area significantly decreased in mac-p27Tg. The inflammatory cytokines were also reduced in mac-p27Tg. We found that the local macrophage proliferation could be one of the common underlying pathophysiological features in the formation and the progression of atherosclerosis. Our results might lead to the control of the macrophage proliferation as the therapeutic target for atherosclerotic disease.

Research Products

• [Journal Article] Acetate alters expression of genes involved in beige adipogenesis in 3T3-L1 cells and obese KK-Ay mice (2016)
  • Author(s): Hanatani S, Motoshima H, Takaki Y, Kawasaki S, Igata M, Matsumura T, Kondo T, Senokuchi T, Ishii N, Kawashima J, Kukidome D, Shimoda S, Nishikawa T, Araki E
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 59 Issue: 3 Pages: 207-214
  • DOI: 10.3164/jcbn.16-23
  • NAID: 130005268723
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Journal Article] Insulin requirement profiles in Japanese hospitalized subjects with type 2 diabetes treated with basal-bolus insulin therapy. (2015)
  • Author(s): Shimoda S, Okubo M, Koga K, Sekigami T, Kawashima J, Kukidome D, Igata M, Ishii N, Shimakawa A, Matsumura T, Motoshima H, Furukawa N, Nishida K, Araki E
  • Journal Title: Endocr J Volume: 62 Pages: 209-216
  • NAID: 130004704365
  • Peer Reviewed
• [Journal Article] Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation. (2015)
  • Author(s): Fukuda K, Matsumura T, Senokuchi T, Ishii N, Kinoshita H, Yamada S, Murakami S, Nakao S, Motoshima H, Kondo T, Kukidome D, Kawasaki S, Kawada T, Nishikawa T, Araki E
  • Journal Title: Biochem Biophys Res Commun Volume: 457 Pages: 23-30
  • Peer Reviewed
• [Journal Article] 糖尿病のすべて 血糖管理目標とエビデンス. (2015)
  • Author(s): 石井規夫, 荒木栄一
  • Journal Title: 医学のあゆみ Volume: 252(5) Pages: 521-529
• [Journal Article] いま知っておきたい！内科最新トピックス 糖尿病治療薬をどう使い分けるか. (2015)
  • Author(s): 石井規夫, 荒木栄一
  • Journal Title: 内科 Volume: 116(6) Pages: 919-925
• [Journal Article] 特集:糖尿病治療新時代-糖尿病治療のupdate- 図説:糖尿病治療薬の作用機序 (2015)
  • Author(s): 石井規夫, 荒木栄一
  • Journal Title: 日本臨床 Volume: 第73巻第12号,
• [Presentation] Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, suppresses the progression of atherosclerosis in diabetic apoE-deficient mice. (2016)
  • Author(s): Murakami S, Matsumura T, Senokuchi T, Ishii N, Fukuda K, Nishida S, Araki E
  • Organizer: 第24回日本血管生物医学会
  • Place of Presentation: 長崎
  • Year and Date: 2016-12-08
• [Presentation] Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, suppresses the progression of atherosclerosis in diabetic apoE-deficient mice. (2016)
  • Author(s): Murakami S, Matsumura T, Senokuchi T, Ishii N, Fukuda K, Yamada S, Morita Y, Nishida S, Sato M, Motoshima H, Kondo T, Araki E
  • Organizer: The 8th AASD Scientific Meeting
  • Place of Presentation: Taipei International Convention Center, Taipei, Taiwan
  • Year and Date: 2016-10-27
  • Int'l Joint Research
• [Presentation] ストレプトゾトシン誘発糖尿病apoE欠損マウスにおいてエンパクリフロジンは大血管症進展を抑制する. (2016)
  • Author(s): 村上彩子, 松村剛, 瀬ノ口隆文, 石井規夫, 福田一起, 山田沙理恵, 守田雄太郎, 西田周平, 久木留大介, 本島寛之, 近藤龍也, 荒木栄一
  • Organizer: 第31回日本糖尿病合併症学会
  • Place of Presentation: 宮城
  • Year and Date: 2016-10-07
• [Presentation] ストレプトゾトシン誘発糖尿病apoE欠損マウスを用いたエンパクリフロジンによる大血管症進展抑制効果の検討. (2016)
  • Author(s): 村上彩子, 松村剛, 瀬ノ口隆文, 石井規夫, 木下博之, 福田一起, 山田沙理恵, 佐藤美希，本島寛之，近藤龍也, 荒木栄一
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 京都
  • Year and Date: 2016-05-19
• [Remarks] Kumamoto University research profiles
  • URL: https://kumamoto.pure.elsevier.com/ja/publications/acetate-alters-expression-of-genes-involved-in-beige-adipogenesis