Role for mechanical stress in lung and airway remodeling

• Project/Area Number: 19689017
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Nagoya University
• Principal Investigator: ITO Satoru Nagoya University, 医学部・附属病院, 助教 (60378073)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2007: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 気管支喘息 / リモデリング / メカニカルストレス / ARDS / TRP / カルシウムイオン / 気道平滑筋 / メカノトランスダクション / IL-8 / 肺微小血管内皮 / 呼吸生理 / メンソール / エンドセリン

Research Abstract

We demonstrated that mechanical stretch activates Ca^<2+> influx via stretch-activated channels and induces production of cytokine/chemokines (IL-6, IL-8, and MCP-1) in human airway smooth muscle cells and pulmonary microvascular endothelial cells. Thus, excessive mechanical strain would contribute to the pathogenesis of lung and airway remodeling via altering cellular properties of pulmonary cells.

Research Products

• [Journal Article] Mechanical stretch enhances IL-8 production in pulmonary microvascular endothelial cells. (2009)
  • Author(s): Iwaki M, Ito S, Morioka M, Iwata S, Numaguchi Y, Ishii M, Kondo M, Kume H, Naruse K, Sokabe M, Hasegawa Y.
  • Journal Title: Biochem Biophys Res Commun 389 Pages: 531-536
  • Peer Reviewed
• [Journal Article] Ion channel regulation of intracellular calcium and airway smooth muscle function. (2009)
  • Author(s): Perez-Zoghbi JF, Karner C, Ito S, Alrashdan YA, Shepherd M, Sanderson M.
  • Journal Title: Pul Pharmacol Ther 22(Review) Pages: 388-397
  • Peer Reviewed
• [Journal Article] Regulation of endothelin-1-induced interleukin-6 production by Ca^<2+> influx in human airway smooth muscle cells. (2009)
  • Author(s): Iwata S, Ito S, Iwaki M, Kondo M, Sashio T, Takeda N, Sokabe M, Hasegawa Y, Kume H.
  • Journal Title: Eur J Pharmacol 605 Pages: 15-22
  • Peer Reviewed
• [Journal Article] Role of Ca^<2+> mobilization and Ca^<2+> sensitization in 8-iso-PGF2α-Induced contraction in airway smooth muscle. (2009)
  • Author(s): Shiraki A, Kume H, Oguma T, Makino Y, Ito S, Shimokata K, Honjo H, Kamiya K.
  • Journal Title: Clin Exp Allergy 39 Pages: 236-245
  • Peer Reviewed
• [Journal Article] Regulation of endothelin-1-induced interleukin-6 production by Ca^<2+> influx in human airway smooth muscle cells (2009)
  • Author(s): Iwata S, et al.
  • Journal Title: Eur J Pharmacol 605 Pages: 15-22
  • Peer Reviewed
• [Journal Article] Ion channel regulation of intracellular calcium and airway smooth muscle function. (Review) (2009)
  • Author(s): Perez-Zoghbi JF, et al.
  • Journal Title: Pul Pharmacol Ther 22 Pages: 388-397
  • Peer Reviewed
• [Journal Article] Mechanical stretch enhances IL-8 production in pulmonary microvascular endothelial cells (2009)
  • Author(s): Iwaki M, et al.
  • Journal Title: Biochem Biophys Res Commun 389 Pages: 531-536
  • Peer Reviewed
• [Journal Article] Actin cytoskeleton regulates stretch- activated Ca^<2+> influx in human pulmonary microvascular endothelial cells (2009)
  • Author(s): Ito S, et al.
  • Journal Title: Am J Respir Cell Mol Biol (online publish) Doi : 10.1165/rcmb.2009-0073OC
  • Peer Reviewed
• [Journal Article] Role of Ca^<2+> mobilization and Ca^<2+> sensitization in 8-iso-PGF2α-Induced contraction in airway smooth muscle (2009)
  • Author(s): Shiraki A, et.al.
  • Journal Title: Clin Exp Allergy 39 Pages: 236-245
  • Peer Reviewed
• [Journal Article] Regulation of endothelin-1-induced interleukin-6 production by Ca^<2+> influx in human airway smooth muscle cells (2009)
  • Author(s): Iwata S, et.al.
  • Journal Title: Eur J Pharmacol (Online publish)
  • Peer Reviewed
• [Journal Article] Inhibition by the cold receptor agonists menthol and icilin of airway smooth muscle contraction. (2008)
  • Author(s): Ito S, Kume H, Shiraki A, Kondo M, Makino Y, Kamiya K, Hasegawa Y.
  • Journal Title: Pulm Pharmacol Ther 21 Pages: 812-817
  • Peer Reviewed
• [Journal Article] A novel Ca^<2+> influx pathway activated by mechanical stretch in human airway smooth muscle cells. (2008)
  • Author(s): Ito S, Kume H, Naruse K, Kondo M, Takeda N, Iwata S, Hasegawa Y, Sokabe M.
  • Journal Title: Am J Respir Cell Mol Biol 38 Pages: 407-413
  • Peer Reviewed
• [Journal Article] A novel Ca^<2+> influx pathway -activated by mechanical stretch in human airway smooth muscle cells (2008)
  • Author(s): Ito S, et.al.
  • Journal Title: Am J Respir Cell Mol Biol 38 Pages: 407-413
  • Peer Reviewed
• [Journal Article] Inhibition by the cold receptor agonists menthol and icilin of airway smooth muscle contraction (2008)
  • Author(s): Ito S, et.al.
  • Journal Title: Pul Pharmacol Ther 21 Pages: 812-817
  • Peer Reviewed
• [Journal Article] Ion channel regulation of intracellular calcium and airway smooth muscle function. (Review) (2008)
  • Author(s): Perez-Zoghbi JF, et.al.
  • Journal Title: Pul Pharmacol Ther (Online publish)
  • Peer Reviewed
• [Journal Article] Roles of P2X receptors and Ca^<2+> sensitization in extracellular adenosine triphosphate-induced hyperresponsiveness in airway smooth muscle. (2007)
  • Author(s): Oguma T, et al.
  • Journal Title: Clin Exp Allergy 37 Pages: 893-900
  • Peer Reviewed
• [Journal Article] Actin cytoskeleton regulates stretch-activated Ca^<2+> influx in human pulmonary microvascular endothelial cells.
  • Author(s): Ito S, Suki B, Kume H, Numaguchi Y, Ishii M, Iwaki M, Kondo M, Naruse K, Hasegawa Y, Sokabe M.
  • Journal Title: Am J Respir Cell Mol Biol
  • Peer Reviewed
• [Presentation] ヒト肺微小血管内皮細胞におけるストレッチ活性型Ca^<2+>流入とTRPV-4チャネルの関連 (2009)
  • Author(s): 伊藤理、他
  • Organizer: 第59回日本アレルギー学会秋季学術大会
  • Place of Presentation: 秋田
  • Year and Date: 2009-10-29
• [Presentation] 肺微小血管内皮細胞におけるストレッチ活性型Ca^<2+>流入とTRPV4チャネルの関連 (2009)
  • Author(s): 伊藤理, 他.
  • Organizer: 第59回日本アレルギー学会秋季学術大会
  • Place of Presentation: 秋田
  • Year and Date: 2009-10-29
• [Presentation] Role of Ca^<2+> influx pathways in airway smooth muscle cell functions. (2009)
  • Author(s): Ito S, et al.
  • Organizer: The 49^<th> Annual Meeting of the Japanese Respiratory Society
  • Place of Presentation: Tokyo
  • Year and Date: 2009-06-14
• [Presentation] ヒト肺微小血管内皮におけるstretch-activated Ca^<2+>流入の制御機構:アクチン細胞骨格の役割. (2009)
  • Author(s): 伊藤理、他
  • Organizer: 第49回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2009-06-13
• [Presentation] Actin cytoskeleton regulates mechanical stretch-activated Ca^<2+> influx in human lung microvascular endothelial cells. (2009)
  • Author(s): Ito S, et al.
  • Organizer: ATS 2009 International Conference
  • Place of Presentation: San Diego, California, USA
  • Year and Date: 2009-05-17
• [Presentation] Mechanical stretch activates Ca^<2+> influx in human lung microvascular end othelial cells. (2009)
  • Author(s): Ito S, et al.
  • Organizer: ATS 2009 International Conference
  • Place of Presentation: San Diego, USA
• [Presentation] 肺微小血管内皮細胞におけるストレッチCa^<2+>流入機構 (2009)
  • Author(s): 伊藤理, 他.
  • Organizer: 第49回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
• [Presentation] Mechanical stretch activates Ca^<2+> influx in human lung microvascular endothelial cells. (2009)
  • Author(s): Ito S, et al
  • Organizer: 第49回日本呼吸器学会学術講演会(Enghsh Mini-symposium)
  • Place of Presentation: 東京
• [Presentation] 気道平滑筋細胞の機能解析:細胞内Ca^<2+>シグナルの役割 (2008)
  • Author(s): 伊藤理、他
  • Organizer: 第58回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-28
• [Presentation] 気道平滑筋細胞の機能解析 : 細胞内Ca^<2+>シグナルの役割 (2008)
  • Author(s): 伊藤理, 他
  • Organizer: 第58回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-28
• [Presentation] ヒト微小血管内皮細胞におけるCa^<2+>入機構 (2008)
  • Author(s): 伊藤理、他
  • Organizer: 第58回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-27
• [Presentation] ヒト肺微小血管内皮細胞におけるCa^<2+>流入機構 (2008)
  • Author(s): 伊藤理, 他
  • Organizer: 第58回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-27
• [Presentation] ヒト微小血管内皮細胞におけるstretch-activated Ca^<2+> influxの制御 (2008)
  • Author(s): 伊藤理、他
  • Organizer: 第48回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸
  • Year and Date: 2008-06-17
• [Presentation] ヒト肺微小血管内皮細胞におけるstretch-activated Ca^<2+> influxの制御 (2008)
  • Author(s): 伊藤理, 他
  • Organizer: 第48回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸
  • Year and Date: 2008-06-17
• [Presentation] A novel Ca^<2+> influx pathway activated by mechanical stretch in human airway smooth muscle cells. (2008)
  • Author(s): 伊藤理
  • Organizer: 第48回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸
  • Year and Date: 2008-06-15
• [Presentation] A novel Ca^<2+> influx pathway activated by mechanical stretch in human airway smooth muscle cells (2008)
  • Author(s): 伊藤理
  • Organizer: 第48回日本呼吸器学会学術講演会「学会奨励賞受賞講演」
  • Place of Presentation: 神戸
  • Year and Date: 2008-06-15
• [Presentation] Mechanical stretch activates Ca^<2+> influx in human lung microvascular endothelial cells. (2008)
  • Author(s): Ito S, et al.
  • Organizer: ATS 2008 International Conference
  • Place of Presentation: Toronto, Ontario, Canada
  • Year and Date: 2008-05-21
• [Presentation] Mechanical stretch activates Ca^<2+> influx in human lung microvascular endothelial cells (2008)
  • Author(s): Ito S, et.al.
  • Organizer: ATS 2008 International Conference
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2008-05-21
• [Presentation] Mechanobiology of airway smooth muscle cells: A novel Ca^<2+> influx pathway activated by mechanical stretch. (2007)
  • Author(s): Ito S, et al.
  • Organizer: 6th International Young Investigators' Symposium on Smooth Muscle
  • Place of Presentation: Sydney, NSW, Australia
  • Year and Date: 2007-11-07
• [Presentation] Mechanobiology of airway smooth muscle cells : a novel Ca^<2+> influx pathway activated by mechanical stretch. (2007)
  • Author(s): Ito S, et al.
  • Organizer: 6th International Young Investigators' Symposium on Smooth Muscle
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2007-11-07
• [Presentation] A role of the cold receptor for menthol-induced relaxation of airway smooth muscle. (2007)
  • Author(s): Ito S, et al.
  • Organizer: ATS 2007 International Conference
  • Place of Presentation: San Francisco, California, USA
  • Year and Date: 2007-05-22
• [Presentation] Effects of airway and tissue heterogeneity for partitioning of airway and tissue properties in normal mice. (2007)
  • Author(s): Ito S, et al.
  • Organizer: ATS 2007 International Conference
  • Place of Presentation: San Francisco, California, USA
  • Year and Date: 2007-05-20
• [Presentation] Mentholは寒冷受容体を介して気道平滑筋を弛緩させる (2007)
  • Author(s): 伊藤理、他
  • Organizer: 第47回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2007-05-12
• [Presentation] English Mini Symposium (2007)
  • Author(s): Ito S, et al.
  • Organizer: The 47^<th> Annual Meeting of the Japanese Respiratory Society
  • Place of Presentation: Tokyo
  • Year and Date: 2007-05-11
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/medical/102/p10218.html
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/medical/102/p10218.html
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/medical/102/p10218.html
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/medical/102/p10218.html