Identification and characterization of muscle-derived renal protective factors

• Project/Area Number: 26461147
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kumamoto University
• Principal Investigator: Izumiya Yasuhiro 熊本大学, 大学院生命科学研究部(医), 助教 (10515414)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 骨格筋 / 分泌因子 / 腎保護作用 / 血管新生 / 慢性腎臓病

Outline of Final Research Achievements

Muscle wasting is frequently observed in patients with cardiovascular and renal disease. We investigated the mechanism by which maintaining muscle mass protects these diseases. We utilized skeletal muscle-specific, inducible Akt1 transgenic (Akt1 TG) mouse that promotes the growth of functional muscle. Tissue damages induced by renal injury were decreased in Akt1 TG mice compared to WT mice. The attenuation of renal damage by myogenic Akt1 activation was accompanied by the activating phosphorylation of eNOS in the kidney. We comprehensively analyzed muscle-derived factors by proteome analysis. We identified Heme oxygenase-1 (HO-1) and Thrombospondin-2 (TSP-2) as a potential factor. We found that endothelial cells and macrophage was a major source of HO-1. We also found that TSP-2 could be a potential biomarker in patients with heart failure. Our data support the concept that maintaining muscle mass may improve clinical outcome in patients with cardiovascular and kidney disease.

Research Products

• [Journal Article] A simple sarcopenia screening test predicts future adverse events in patients with heart failure. (2016)
  • Author(s): Onoue Y, Izumiya Y, Hanatani S, Tanaka T, Yamamura S, Kimura Y, Araki S, Sakamoto K, Tsujita K, Yamamoto E, Yamamuro M, Kojima S, Kaikita K, Hokimoto S.
  • Journal Title: International Journal of Cardiology Volume: 215 Pages: 301-306
  • DOI: 10.1016/j.ijcard.2016.04.128
  • Peer Reviewed / Open Access
• [Journal Article] Reduced trans-mitral a-wave velocity predicts the presence of wild-type transthyretin amyloidosis in elderly patients with left ventricular hypertrophy. (2016)
  • Author(s): 山村智、泉家康宏、石田俊史、尾上喜郎、木村優一、花谷信介、荒木智、藤末昴一郎、末田大輔、金澤尚徳、高潮征爾、宇宿弘輝、菅村公一、坂本憲治、山本英一郎、山室惠、安田久代、小島淳、海北幸一、掃本誠治、小川久雄、辻田賢一
  • Journal Title: Heart Vessels. Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Expression of Let-7 family microRNA in skin correlates negatively with severity of pulmonary hypertension in patients with systemic scleroderma. (2015)
  • Author(s): 泉家康宏、神人正寿、木村優一、Zhongzhi Wang、尾上喜郎、花谷信介、荒木智、尹浩信、小川久雄
  • Journal Title: IJC Heart and Vasculature. Volume: 8 Pages: 98-102
  • DOI: 10.1016/j.ijcha.2015.06.006
  • Peer Reviewed
• [Journal Article] Akt1-Mediated Fast/glycolytic Skeletal Muscle Growth Attenuates Renal Damage in Experimental Kidney Disease. (2014)
  • Author(s): 花谷信介、泉家康宏、荒木智、六反田拓、木村優一、Kenneth Walsh、小川久雄
  • Journal Title: J Am Soc Nephrol. Volume: 25 Issue: 12 Pages: 2800-11
  • DOI: 10.1681/asn.2013091025
  • Peer Reviewed / Open Access
• [Presentation] Akt1による骨格筋肥大はヘムオキシゲナーゼ1を介して下肢虚血後の血管新生を促進する (2016)
  • Author(s): 泉家康宏、尾上喜郎、花谷信介、山村智、石田俊史、木村優一、荒木智、辻田賢一
  • Organizer: Cardiovascular and Metabolic Week2016(CVMW)
  • Place of Presentation: 東京コンベンションホール
  • Year and Date: 2016-12-16
• [Presentation] Akt1-mediated Skeletal Muscle Growth Enhances Blood Flow Recovery after Hind Limb Ischemia by Activating Heme Oxygenase-1 in Macrophage (2016)
  • Author(s): 尾上喜郎、泉家康宏、花谷信介、石田俊史、山村智、木村優一、荒木智、掃本誠治
  • Organizer: AHA Scientific session 2016
  • Place of Presentation: Ernest N. Morial Convention Center
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Akt1-mediates Skeletal Muscle growth Enhances Blood Flow Recovery after Hind Limb Ischemia by Activating Heme Oxygenase-1 in Macrophage. (2016)
  • Author(s): 泉家康宏、尾上喜郎、花谷信介、木村優一
  • Organizer: 19th International Vascular Biology Meeting
  • Place of Presentation: Sheraton Boston Hotel
  • Year and Date: 2016-10-30
  • Int'l Joint Research
• [Presentation] Akt1による骨格筋肥大はマクロファージ由来Heme oxygenase-1を介して下肢虚血後の血管新生能を亢進する (2016)
  • Author(s): 尾上喜郎、泉家康宏、花谷信介、石田俊史、山村智、木村優一、荒木智、海北幸一、掃本誠治、辻田賢一
  • Organizer: 第57回 日本脈管学会総会 YIAセッション
  • Place of Presentation: ホテル日航奈良
  • Year and Date: 2016-10-13
• [Presentation] Akt1による骨格筋肥大はHeme oxygenase-1を介して下肢虚血後の血管新生を促進する (2016)
  • Author(s): 尾上喜郎、泉家康宏、花谷信介、山村智、木村優一、荒木智、海北幸一、掃本誠治
  • Organizer: 第120回日本循環器学会九州地方会 YIAセッション
  • Place of Presentation: ホルトホール大分
• [Presentation] Expression of Let-7 Family microRNAs in Skin Correlates Negatively with Severity of Pulmonary Hypertension in Patients with Systemic Scleroderma (2015)
  • Author(s): 泉家康宏、木村優一、山村智、尾上喜郎、花谷信介、荒木智、小川久雄
  • Organizer: AHA Scientific session 2015
  • Place of Presentation: Orange County Convention Center, オーランド、米国
  • Year and Date: 2015-11-09
• [Presentation] Identification of muscle-derived factors contributing to beneficial effect of cardiac rehabilitation (2015)
  • Author(s): 泉家康宏、尾上喜郎、木村優一、花谷信介、荒木智、田中朋子、小川久雄
  • Organizer: 第21回日本心臓リハビリテーション学会学術集会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2015-07-19
  • Invited
• [Presentation] 骨格筋由来因子という観点から見た心臓リハビリの有用性 (2015)
  • Author(s): 泉家康宏、山村智、尾上喜郎、木村優一、花谷信介、荒木智、小川久雄
  • Organizer: 第2回日本脳卒中学会学術集会
  • Place of Presentation: ホテルクレメント徳島
  • Year and Date: 2015-06-13
  • Invited
• [Presentation] 骨格筋由来ホルモンという観点から見た運動療法の有用性 (2015)
  • Author(s): 泉家康宏、尾上喜郎、木村優一、花谷信介、荒木智、小川久雄
  • Organizer: 第32回小倉ライブデモンストレーション心臓リハビリテーションコース
  • Place of Presentation: 西日本総合展示場
  • Year and Date: 2015-05-17
  • Invited
• [Presentation] Type II fast/glycolytic skeletal muscle growth attenuates cardio-renal injury by activating eNOS signaling in remote tissue via endocrine fashion (2015)
  • Author(s): 泉家康宏、花谷信介、荒木智、木村優一、尾上喜郎、小川久雄
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2015-04-24
  • Invited
• [Presentation] 骨格筋由来分泌因子を介した骨格筋-腎連関による新規腎保護戦略の探索 (2015)
  • Author(s): 泉家康宏、尾上喜郎、木村優一、花谷信介、六反田拓、荒木智、小川久雄
  • Organizer: 日本腎臓リハビリテーション学会学術集会
  • Place of Presentation: 都市センターホテル
  • Year and Date: 2015-03-21
  • Invited
• [Presentation] 骨格筋由来ホルモンという観点から見た運動療法の有用性 (2014)
  • Author(s): 泉家康宏、尾上喜郎、木村優一、花谷信介、六反田拓、荒木智、小川久雄
  • Organizer: ARIA 2014 心臓リハビリテーションコース
  • Place of Presentation: 電気ビル共創館
  • Year and Date: 2014-11-23
  • Invited
• [Presentation] Akt1過剰発現による骨格筋肥大は腎臓病モデルマウスの腎障害を軽減する (2014)
  • Author(s): 花谷信介, 泉家康宏, 木村優一, 尾上喜郎, 荒木智, 小川久雄
  • Organizer: 心血管内分泌代謝学会総会 YIAセッション
  • Place of Presentation: 横浜市開港記念会館
  • Year and Date: 2014-11-21
• [Presentation] Akt1-Mediated Fast/glycolytic Skeletal Muscle Growth Attenuates Renal Damagein Experimental Kidney Disease (2014)
  • Author(s): 花谷信介、泉家康宏、荒木智、六反田拓、木村優一、小川久雄
  • Organizer: 日本高血圧学会総会 YIAセッション
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2014-10-17
• [Presentation] 骨格筋からみた循環器疾患治療戦略 (2014)
  • Author(s): 泉家康宏、花谷信介、木村優一、荒木智、小川久雄
  • Organizer: 日本循環制御医学会総会
  • Place of Presentation: 九州大学医学部 百年講堂
  • Year and Date: 2014-07-04
  • Invited