Role of miRNAs in the development of bronchial smooth muscle hyperresponsiveness in allergic asthma

• Project/Area Number: 23590118
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Hoshi University
• Principal Investigator: CHIBA Yoshihiko 星薬科大学, 薬学部, 准教授 (00287848)
• Co-Investigator(Kenkyū-buntansha): SAKAI Hiroyasu 星薬科大学, 薬学部, 講師 (00328923)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: アレルギー性気管支喘息 / 気道過敏性 / 気管支平滑筋 / microRNA (miRNA) / miR-140 / RhoA / CD38 / Interleukin-13 (IL-13) / miR-140-5p / TLR4 / サイトカイン / interleukin-13 (IL-13)

Research Abstract

Current study was carried out to make clear the mechanism(s) of development of airway hyperresponsiveness in asthmatics. In bronchial smooth muscles of mice with allergic asthma, an up-regulation of RhoA protein and a down-regulation of miR-140-3p were observed. In cultured human bronchial smooth muscle cells, an up-regulation of RhoA protein was observed when the function of endogenous miR-140-3p was inhibited by its antagomir. Treatment of the cells with interleukin-13 caused an up-regulation of RhoA protein and a down-regulation of miR-140-3p. These findings suggest that RhoA protein expression is negatively regulated by miR-140-3p in bronchial smooth muscle cells. The increased expression of interleukin-13 in the airways of asthmatics might, at least in part, contribute to the reduction of miR-140-3p, resulting in an up-regulation of RhoA protein and augmented smooth muscle contraction of the airways.

Research Products

• [Journal Article] The gene expression of aquaporins in various cutaneous tissues of the mouse (2014)
  • Author(s): Sakai, H., Sato, K., Takase, K., Hirosaki, A., Jo, A., Sugiyama, R., Chiba, Y. and Narita, M
  • Journal Title: J. Exp. Integr. Med Volume: 4 Pages: 75-79
• [Journal Article] The gene expression of aquaporins in various cutaneous tissues of the mouse. (2014)
  • Author(s): Sakai H, Sato K, Takase K, Hirosaki A, Jo A, Sugiyama R, Chiba Y, Narita M.
  • Journal Title: J Exp Integr Med. Volume: 4 Pages: 75-79
  • Peer Reviewed
• [Journal Article] Mechanisms of cisplatin-induced muscle atrophy. (2014)
  • Author(s): Sakai H, Sagara A, Arakawa K, Sugiyama R, Hirosaki A, Takase K, Jo A, Sato K, Chiba Y, Yamazaki M, Matoba M, Narita M.
  • Journal Title: Toxicol Appl Pharmacol. Volume: n/a
  • Peer Reviewed
• [Journal Article] Augmented bronchial smooth muscle contractility induced by aqueous cigarette smoke extract in rats. (2014)
  • Author(s): Sakai H, Watanabe A, Fujita A, Misawa M, Narita M, Chiba Y.
  • Journal Title: J Smooth Muscle Res. Volume: n/a
  • NAID: 130004432186
  • Peer Reviewed
• [Journal Article] Interleukin-17A directly acts on bronchial smooth muscle cells and augments the contractility (2014)
  • Author(s): Chiba Y, Tanoue G, Suto R, Suto W, Hanazaki M and Katayama H.
  • Journal Title: Am J Respir Cell Mol Biol Volume: n/a
  • Peer Reviewed
• [Journal Article] Down-regulation of MiR-140-3p Contributes to Up-regulation of CD38 Protein in Bronchial Smooth Muscle Cells (2014)
  • Author(s): Chiba Y, Matsumoto M, Kato Y, et al.
  • Journal Title: Am J Respir Cell Mol Biol Volume: n/a
  • Peer Reviewed
• [Journal Article] Involvement of the Tyr kinase/JNK pathway in carbachol-induced bronchial smooth muscle contraction in the rat (2013)
  • Author(s): Sakai, H., Watanabe, Y., Honda, M., Tsuiki, R. Ueda, Y., Nagai, Y., Narita, M. and Chiba, Y
  • Journal Title: Anesthesiology Volume: 118 Pages: 1076-1085
• [Journal Article] Elevated guanylate cyclase and cyclic-guanosine monophosphate-dependent protein kinase levels in nasal mucosae of antigen-challenged rats (2013)
  • Author(s): Sakai, H., Hara, T., Todoroki, K., Igarashi, Y., Misawa, M., Narita, M. and Chiba, Y
  • Journal Title: Microvasc. Res Volume: 90 Pages: 150-153
• [Journal Article] Involvement of the Tyr kinase/JNK pathway in carbachol-induced bronchial smooth muscle contraction in the rat. (2013)
  • Author(s): Sakai, H., Watanabe, Y., Honda, M., Tsuiki, R. Ueda, Y., Nagai, Y., Narita, M. and Chiba, Y.
  • Journal Title: Anesthesiology Volume: 118 Pages: 1076-1085
  • Peer Reviewed
• [Journal Article] Elevated guanylate cyclase and cyclic-guanosine monophosphate-dependent protein kinase levels in nasal mucosae of antigen-challenged rats. (2013)
  • Author(s): Sakai, H., Hara, T., Todoroki, K., Igarashi, Y., Misawa, M., Narita, M. and Chiba, Y.
  • Journal Title: Microvasc. Res. Volume: 90 Pages: 150-153
  • Peer Reviewed
• [Journal Article] Interleukin-13-induced activation of signal transducer and activator of transcription 6 is mediated by an activation of Janus kinase 1 in cultured human bronchial smooth muscle cells (2012)
  • Author(s): Chiba, Y., Goto, K. and Misawa, M
  • Journal Title: Pharmacol. Rep Volume: 64 Pages: 454-458
• [Journal Article] Matrix metalloproteinases-9 (MMP-9) and -12 are upregulated in the airways of mice with chronic airway inflammation and remodeling (2012)
  • Author(s): Yu, Y., Sakai, H., Misawa, M. and Chiba, Y
  • Journal Title: ISRN Pulmonology 2012 Volume: Article ID 840489 Pages: 7-7
• [Journal Article] Effect of sugammadex on bronchial smooth muscle function in rats (2012)
  • Author(s): Yoshioka, N., Hanazaki, M., Fujita, Y., Nakatsuka, H., Katayama, H. and Chiba, Y
  • Journal Title: J. Smooth Muscle Res Volume: 48 Pages: 59-64
  • NAID: 10030687476
• [Journal Article] Interleukin-13-induced activation of signal transducer and activator of transcription 6 is mediated by an activation of Janus kinase 1 in cultured human bronchial smooth muscle cells. (2012)
  • Author(s): Chiba, Y., Goto, K. and Misawa, M.
  • Journal Title: Pharmacol. Rep. Volume: 64 Pages: 454-458
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinases-9 (MMP-9) and -12 are upregulated in the airways of mice with chronic airway inflammation and remodeling. (2012)
  • Author(s): Yu, Y., Sakai, H., Misawa, M. and Chiba, Y.
  • Journal Title: ISRN Pulmonology Volume: Article ID 840489 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Effect of sugammadex on bronchial smooth muscle function in rats. (2012)
  • Author(s): Yoshioka, N., Hanazaki, M., Fujita, Y., Nakatsuka, H., Katayama, H. and Chiba, Y.
  • Journal Title: J. Smooth Muscle Res. Volume: 48 Pages: 59-64
  • NAID: 10030687476
  • Peer Reviewed
• [Journal Article] Antigen exposure causes activations of signal transducer and activator of transcription 6 (STAT6) and STAT1, but not STAT3, in lungs of sensitized mice (2011)
  • Author(s): Chiba, Y., Todoroki, M. and Misawa, M
  • Journal Title: Immunopharmacol. Immunotoxicol Volume: 33 Pages: 43-48
• [Journal Article] Sphingosine-1-phosphate augments agonist-mediated contraction in bronchial smooth muscles of mice (2011)
  • Author(s): Chiba, Y., Takeuchi, H., Sakai, H. and Misawa, M
  • Journal Title: Pharmacol. Rep Volume: 63 Pages: 544-547
• [Journal Article] Different effects of smoke from heavy and light cigarettes on induction of bronchial smooth muscle hyperresponsiveness in rats (2011)
  • Author(s): Sakai, H., Fujita, A., Watanabe, A., Chiba, Y., Kamei, J. and Misawa, M
  • Journal Title: J. Smooth Muscle Res Volume: 47 Pages: 1-10
  • NAID: 10029134260
• [Journal Article] Involvement of K^+ channels in the augmented nasal venous responsiveness to nitric oxide in rat model of allergic rhinitis (2011)
  • Author(s): Sakai, H., Enzaka, J., Sakai-Oshita, M., Chiba, Y. and Misawa, M
  • Journal Title: Microvas. Res Volume: 81 Pages: 129-134
• [Journal Article] Antigen-challenge influences various transcription factors of rat bronchus : Protein/DNA array study (2011)
  • Author(s): Sakai, H., Hirahara, M., Chiba, Y. and Misawa, M
  • Journal Title: Int. Immunopharmacol. Volume: 11 Pages: 1133-1136
• [Journal Article] Antigen exposure causes activations of signal transducer and activator of transcription 6 (STAT6) and STAT1, but not STAT3, in lungs of sensitized mice. (2011)
  • Author(s): Chiba, Y., Todoroki, M. and Misawa, M.
  • Journal Title: Immunopharmacol. Immunotoxicol. Volume: 33 Pages: 43-48
  • Peer Reviewed
• [Journal Article] Sphingosine-1-phosphate augments agonist-mediated contraction in bronchial smooth muscles of mice. (2011)
  • Author(s): Chiba, Y., Takeuchi, H., Sakai, H. and Misawa, M.
  • Journal Title: Pharmacol. Rep. Volume: 63 Pages: 544-547
  • Peer Reviewed
• [Journal Article] Different effects of smoke from heavy and light cigarettes on the induction of bronchial smooth muscle hyperresponsiveness in rats. (2011)
  • Author(s): Sakai, H., Fujita, A., Watanabe, A., Chiba, Y., Kamei, J. and Misawa, M.
  • Journal Title: J. Smooth Muscle Res. Volume: 47 Pages: 1-10
  • NAID: 10029134260
  • Peer Reviewed
• [Journal Article] Antigen-challenge influences various transcription factors of rat bronchus: Protein/DNA array study. (2011)
  • Author(s): Sakai, H., Hirahara, M., Chiba, Y. and Misawa, M.
  • Journal Title: Int. Immunopharmacol. Volume: 11 Pages: 1133-1136
  • Peer Reviewed
• [Journal Article] Mechanisms of cisplatin-induced muscle atrophy
  • Author(s): Sakai, H., Sagara, A., Arakawa, K., Sugiyama, R., Hirosaki, A., Takase, K., Jo, A., Sato, K., Chiba, Y., Yamazaki, M., Matoba, M. and Narita, M
  • Journal Title: Toxicol. Appl. Pharmacol Volume: (in press)
• [Journal Article] Augmented bronchial smooth muscle contractility induced by aqueous cigarette smoke extract in rats
  • Author(s): Sakai, H., Watanabe, A., Fujita, A., Misawa, M., Narita, M. and Chiba, Y
  • Journal Title: J. Smooth Muscle Res Volume: (in press)
  • NAID: 130004432186
• [Presentation] 培養ヒト気管支平滑筋細胞におけるRhoA発現に対するLIGHTの効果 (2014)
  • Author(s): 千葉義彦, 酒井寛泰, ほか
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Year and Date: 2014-03-30
• [Presentation] アレルギー性気管支喘息時の気管支平滑筋RhoA発現に及ぼすTSLPの役割 (2014)
  • Author(s): 千葉義彦, 酒井寛泰, ほか
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Year and Date: 2014-03-30
• [Presentation] アレルギー性気管支喘息時の気管支平滑筋過敏性発現におけるinterleukin-17の役割 (2014)
  • Author(s): 千葉義彦, 酒井寛泰, ほか
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Year and Date: 2014-03-30
• [Presentation] アレルギー性気管支喘息時の気管支平滑筋TLR4 up-regulationにおけるmiR-140-5pの役割 (2014)
  • Author(s): 千葉義彦, 酒井寛泰, ほか
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Year and Date: 2014-03-30
• [Presentation] 培養ヒト気管支平滑筋細胞におけるinterleukin-17AによるRhoAタンパク質発現の増加 (2014)
  • Author(s): 千葉義彦, 酒井寛泰, ほか
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
  • Year and Date: 2014-03-21
• [Presentation] Effect of rocuronium-sugammadex clathrate on rat airway smooth muscle contraction (2013)
  • Author(s): Yoshihiko Chiba, et al
  • Organizer: Anesthesiology 2013
  • Place of Presentation: CA USA
  • Year and Date: 2013-10-14
• [Presentation] アレルギー気管支喘息時の気管支平滑筋RhoA up-regulationにおけるmiR-140-3pの役割 (2013)
  • Author(s): 千葉義彦, 酒井寛泰, ほか
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-30
• [Presentation] 苦味受容体であるT2R8遺伝子の組織発現分布ならびにT2R8を介した平滑筋弛緩作用 (2013)
  • Author(s): 千葉義彦, 酒井寛泰, ほか
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-30
• [Presentation] アレルギー性気管支喘息時の気管支平滑筋細胞においてmiR-140-3p down-regulationがCD38 up-regulationをもたらす (2013)
  • Author(s): 千葉義彦, 酒井寛泰, ほか
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2013-03-22
• [Presentation] Effects of systemic treatment with immunosuppressants on rat airway smooth muscle contraction (2012)
  • Author(s): Yoshihiko Chiba, et al
  • Organizer: Anesthesiology 2012
  • Place of Presentation: DC USA
  • Year and Date: 2012-10-15
• [Presentation] スガマデクスが気道平滑筋収縮に及ぼす影響 (2012)
  • Author(s): 千葉義彦, ほか
  • Organizer: 日本麻酔科学会第59回学術集会.
  • Place of Presentation: 神戸
  • Year and Date: 2012-06-08
• [Presentation] 気道の薬理学的研究(第353報):培養ヒト気管支平滑筋細胞のIL-13誘発STAT6活性化におけるJAK1の関与 (2012)
  • Author(s): 千葉義彦, ほか
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-29
• [Presentation] 気道の薬理学的研究(第352報): Soluble epoxide hydrolase阻害薬による抗原誘発気管支平滑筋過敏性発現の抑制 (2011)
  • Author(s): 千葉義彦, 酒井寛泰, ほか
  • Organizer: 第125回日本薬理学会関東部会
  • Place of Presentation: 千葉
  • Year and Date: 2011-10-15
• [Presentation] Effects of systemic treatment with immunosuppressants on rat airway smooth muscle contraction (2011)
  • Author(s): Yoshihiko Chiba, et al
  • Organizer: Anesthesiology 2011
  • Place of Presentation: CA USA
• [Presentation] Effects of systemic treatment with immunosuppressants on rat airway smooth muscle contraction. (2011)
  • Author(s): Hanazaki, M., Katayama, H., Nakatsuka, H., Fujita, Y., Chiba, Y.
  • Organizer: Anesthesiology 2011
  • Place of Presentation: Chicago, Illinois, USA
• [Presentation] 気道の薬理学的研究 (第 352 報): Soluble epoxide hydrolase阻害薬による抗原誘発気管支平滑筋過敏性発現の抑制 (2011)
  • Author(s): 石渡聡美, 宮澤 綾, 渋谷 彩, 岡本祐二, 酒井寛泰, 三澤美和, 成田 年, 千葉義彦
  • Organizer: 第125回日本薬理学会関東部会
  • Place of Presentation: 千葉県船橋市
• [Presentation] Effect of rocuronium-sugammadex clathrate on rat airway smooth muscle contraction
  • Author(s): Motohiko Hanazaki, Naoki Yoshioka, Yoshihisa Fujita, Hideki Nakatsuka, Hiroshi Katayama, Yoshihiko Chiba
  • Organizer: Anesthesiology 2013
  • Place of Presentation: San Francisco, CA, USA
• [Presentation] 培養ヒト気管支平滑筋細胞におけるinterleukin-17AによるRhoAタンパク質発現の増加
  • Author(s): 千葉義彦、田上 元、清水一樹、須藤怜奈、須藤 航、團野駿太、中原孝史、松本麻友美、加藤靖菜、安藤桂子、酒井寛泰、成田 年、花崎元彦、片山 浩
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台国際センター
• [Presentation] 培養ヒト気管支平滑筋細胞におけるRhoA発現に対するLIGHTの効果
  • Author(s): 千葉義彦、須藤怜奈、清水一樹、須藤 航、田上 元、團野駿太、中原孝史、加藤靖菜、安藤桂子、松本麻友美、酒井寛泰、成田 年、花崎元彦、片山 浩
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本大学
• [Presentation] アレルギー性気管支喘息時の気管支平滑筋 RhoA 発現に及ぼす TSLP の役割
  • Author(s): 千葉義彦、須藤 航、清水一樹、須藤怜奈、田上 元、團野駿太、中原孝史、加藤靖菜、安藤桂子、松本麻友美、酒井寛泰、成田 年、花崎元彦、片山 浩
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本大学
• [Presentation] アレルギー性気管支喘息時の気管支平滑筋過敏性発現における interleukin-17 の役割
  • Author(s): 千葉義彦、田上 元、清水一樹、須藤怜奈、須藤 航、團野駿太、中原孝史、加藤靖菜、安藤桂子、松本麻友美、酒井寛泰、成田 年、花崎元彦、片山 浩
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本大学
• [Presentation] アレルギー性気管支喘息時の気管支平滑筋 TLR4 up-regulation における miR-140-5p の役割
  • Author(s): 千葉義彦、中原孝史、清水一樹、須藤怜奈、須藤 航、田上 元、團野駿太、加藤靖菜、安藤桂子、松本麻友美、酒井寛泰、成田 年、花崎元彦、片山 浩
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本大学
• [Presentation] スガマデクスが気道平滑筋収縮に及ぼす影響
  • Author(s): 吉岡直紀、花崎元彦、片山 浩、中塚秀輝、藤田喜久、千葉義彦
  • Organizer: 日本麻酔科学会第59回学術集会
  • Place of Presentation: 神戸市
• [Presentation] Effect of Sugammadex on Rat Airway Smooth Muscle Contraction
  • Author(s): Motohiko Hanazaki, Naoki Yoshioka, Yoshihisa Fujita, Hideki Nakatsuka, Hiroshi Katayama, Yoshihiko Chiba
  • Organizer: Anesthesiology 2012
  • Place of Presentation: Washington D.C., USA
• [Presentation] アレルギー性気管支喘息時の気管支平滑筋細胞において miR-140-3p down-regulation が CD38 up-regulation をもたらす
  • Author(s): 千葉義彦、松本麻友美、加藤靖菜、安藤桂子、清水一樹、須藤怜奈、須藤 航、田上 元、團野駿太、中原孝史、花崎元彦、片山 浩、酒井寛泰、成田 年
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡市
• [Presentation] アレルギー気管支喘息時の気管支平滑筋RhoA up-regulationにおけるmiR-140-3pの役割
  • Author(s): 千葉義彦、加藤靖菜、安藤桂子、松本麻友美、清水一樹、須藤怜奈、須藤 航、田上 元、團野駿太、中原孝史、花崎元彦、片山 浩、酒井寛泰、成田 年
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜市
• [Remarks]
  • URL: http://www.hoshi.ac.jp/home/kyoiku/kyoushitsuhgaid/25kyoushitsu.seibutsu.html
• [Remarks] 所属研究室ホームページ
  • URL: http://www.hoshi.ac.jp/home/kyoiku/kyoushitsuhgaid/25kyoushitsu.seibutsu.html
• [Remarks] 研究業績等
  • URL: http://www.hoshi.ac.jp/home/kyoiku/KyoinJiseki/chiba.pdf
• [Remarks] 所属研究室ホームページ
  • URL: http://www.hoshi.ac.jp/home/kyoiku/kyoushitsuhgaid/25kyoushitsu.seibutsu.html
• [Remarks] 研究業績等
  • URL: http://www.hoshi.ac.jp/home/kyoiku/KyoinJiseki/chiba.pdf
• [Remarks]
  • URL: http://www.hoshi.ac.jp/home/kyoiku/kyoushitsuhgaid/25kyoushitsu.seibutsu.html
• [Remarks]
  • URL: http://www.hoshi.ac.jp/home/kyoiku/KyoinJiseki/chiba.pdf