The roles of NF-κB pathway in the endothelium

• Project/Area Number: 22790681
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Tohoku University
• Principal Investigator: HASEGAWA Yutaka 東北大学, 病院, 助教 (90451559)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: NF-κB / 血管内皮 / 酸化ストレス / 寿命 / NF-kB

Research Abstract

We generated transgenic mice expressing dominant-negative IκB under the Tie2 promoter/enhancer (E-DNIκB mice). These mice exhibited functional inhibition of NF-κB signaling specifically in endothelial cells. Although E-DNIκB mice displayed no overt phenotypic changes when young and lean, they were protected from the development of insulin resistance associated with obesity. Obesity-induced macrophage infiltration into adipose tissue and plasma oxidative stress markers were decreased, while blood flow and mitochondrial contents in muscle and active-phase locomotor activity were increased in E-DNIκB mice. In addition to inhibition of obesity-related metabolic deteriorations, blockade of endothelial NF-κB signaling prevented age-related insulin resistance and vascular senescence and, notably, prolonged lifespan. These anti-aging phenotypes were also associated with decreased oxidative stress markers, increased muscle blood flow, enhanced active-phase locomotor activity.

Research Products

• [Journal Article] Blockade of the NF-κB pathway in the endothelium prevents insulin resistance and prolongs lifespans (2012)
  • Author(s): Hasegawa Y, Saito T, Ogihara T, Ishigaki Y, Yamada T, Imai J, Uno K, Gao J, Kaneko K, Shimosawa T, Asano T, Fujita T, Oka Y, Katagiri H
  • Journal Title: Circulation Volume: 125 Pages: 1122-1133
• [Journal Article] Blockade of the Nuclear Factor-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Life Spans (2012)
  • Author(s): Hasegawa Y, Saito T, Ogihara T, Ishigaki Y, Yamada T, Imai J, Uno K, Gao J, Kaneko K, Shimosawa T, Asano T, Fujita T, Oka Y, Katagiri H
  • Journal Title: Circulation Volume: 125 Pages: 1122-1133
  • Peer Reviewed
• [Journal Article] Blockade of the NF-kappaB pathway in the endothelium prevents insulin resistance and prolongs lifespans (2011)
  • Author(s): Hasegawa Y, Saito T, Ogihara T, Ishigaki Y, Yamada T, Imai J, Uno K, GaoJ, Kaneko K, Shimosawa T, Asano T, Fujita T Oka Y, Katagiri H
  • Journal Title: Circulation
• [Journal Article] Involvement of Endoplasmic Stress Protein C/EBP Homologous Protein in Arteriosclerosis Acceleration With Augmented Biological Stress Responses (2011)
  • Author(s): Gao J, Ishigaki Y, Yamada T, Kondo K, Yamaguchi S, Imai J, Uno K, Hasegawa Y, Sawada S, Ishihara H, Oyadomari S, Mori M, Oka Y, Katagiri H
  • Journal Title: Circulation Volume: 124(7) Pages: 830-839
• [Journal Article] Interleukin-6 Enhances Glucose-Stimulated Insulin Secretion From Pancreatic { beta}-Cells : Potential Involvement of the PLC-IP3-Dependent Pathway (2011)
  • Author(s): Suzuki T, Imai J, Yamada T, Ishigaki Y, Kaneko K, Uno K, Hasegawa Y, Ishihara H, Oka Y, Katagiri H
  • Journal Title: Diabetes Volume: 60(2) Pages: 537-547
• [Journal Article] Interleukin-6 enhances glucose-stimulated insulin secretion from pancreatic beta-cells : potential involvement of the PLC-IP3-dependent pathway. (2011)
  • Author(s): Suzuki T, Hasegawa Y
  • Journal Title: Diabetes Volume: 60(2) Pages: 537-547
  • Peer Reviewed
• [Journal Article] Hepatic peroxisome proliferator-activated receptor-{ gamma}-fat-specific protein 27 pathway contributes to obesity-related hypertension via afferent vagal signals. Eur Heart J
  • Author(s): Uno K, Yamada T, Ishigaki Y, Imai J, Hasegawa Y, Gao J, Kaneko K, Matsusue K, Yamazaki T, Oka Y, Katagiri H
  • Journal Title: Eur Heart J
• [Presentation] 経管栄養中に高血糖高浸透圧昏睡にて救急搬入された初回治療2型糖尿病の1例 (2011)
  • Author(s): 鈴木亨, 山口賢, 角田宇衣子, 長谷川豊, 丹治泰裕, 山本淳平, 今井淳太, 山田哲也, 石垣泰, 岡芳知, 片桐秀樹
  • Organizer: 日本糖尿病学会第49回東北地方会
  • Place of Presentation: 仙台
  • Year and Date: 2011-11-05
• [Presentation] 膵腎同時移植によりインスリン量の減量・慢性維持透析治療から離脱できた1型糖尿病の1例 (2011)
  • Author(s): 本間緑, 長谷川豊, 井泉知仁, 澤田正二郎, 石垣泰, 川岸直樹, 関口悟, 里見進, 岡芳知, 片桐秀樹
  • Organizer: 日本糖尿病学会第49回東北地方会
  • Place of Presentation: 仙台
  • Year and Date: 2011-11-05
• [Presentation] 膵動静脈奇形に対する膵全摘後に自家膵島移植を施行した1例 (2011)
  • Author(s): 井泉知仁, 長谷川豊, 山口賢, 角田宇衣子, 澤田正二郎, 後藤昌史, 海野倫明, 里見進, 岡芳知, 片桐秀樹
  • Organizer: 日本糖尿病学会第49回東北地方会
  • Place of Presentation: 仙台
  • Year and Date: 2011-11-05
• [Presentation] 高度肥満に腹腔鏡下袖状胃切除術を施行した2例 (2011)
  • Author(s): 本藏理恵子, 長谷川豊, 近藤敬一, 今井淳太, 山田哲也, 石垣泰, 内藤剛, 柴田近, 岡芳知, 片桐秀樹
  • Organizer: 日本糖尿病学会第49回東北地方会
  • Place of Presentation: 仙台
  • Year and Date: 2011-11-05
• [Presentation] Blockade of the endothelial NF-kB pathway prevents insulin resistance and prolongs lifespan (2011)
  • Author(s): Yutaka Hasegawa, Yoshitomo Oka, Hideki Katagiri
  • Organizer: KEYSTONE SYMPOSIA
  • Place of Presentation: Keystone, Colorado, USA
  • Year and Date: 2011-07-17
• [Presentation] Blockade of the endothelial NF-κB pathway prevents obesity- and age-related insulin resistance and prolongs lifespan (2011)
  • Author(s): Yutaka Hasegawa
  • Organizer: KEYSTONE SYMPOSIA
  • Place of Presentation: Keystone, Colorado, USA
  • Year and Date: 2011-01-16
• [Presentation] エゼチミブの肝機能改善効果の検討 (2011)
  • Author(s): 山本淳平, 石垣泰, 金子慶三, 長谷川豊, 山口賢, 宇野健司, 澤田正二郎, 今井淳太, 山田哲也, 岡芳知, 片桐秀樹
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] 動脈硬化発症・進展におけるWSF1の役割の検討 (2011)
  • Author(s): 高俊弘, 石垣泰, 澤田正二郎, 近藤敬一, 井泉知仁, 宇野健司, 長谷川豊, 山口賢, 金子慶三, 突田壮平, 高橋圭, 今井淳太, 山田哲也, 石原寿光, 岡芳知, 片桐秀樹
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] 褐色脂肪組織における熱産生抑制につながる組織間ネットワーク (2011)
  • Author(s): 突田壮平, 山田哲也, 宇野健司, 高橋圭, 白井勇太, 宗像佑一郎, 金子慶三, 澤田正二郎, 長谷川豊, 今井淳太, 石垣泰, 岡芳知, 片桐秀樹
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] Blockade of the endothelial NF-κB pathway prevents insulin resistance and prolongs lifespan (2011)
  • Author(s): Hasegawa Y, Oka Y, Katagiri H
  • Organizer: Keystone Symposia
  • Place of Presentation: Keystone, Colorado, USA
• [Presentation] 脳死下膵腎同時移植によりインスリン治療から離脱した1型糖尿病の一例 (2010)
  • Author(s): 高橋圭, 長谷川豊, 近藤敬一, 金子慶三, 宇野健司, 今井淳太, 山田哲也, 石垣泰, 片桐秀樹, 里見進, 岡芳知
  • Organizer: 第48回日本糖尿病学会東北地方会
  • Place of Presentation: 仙台
  • Year and Date: 2010-11-06