Tissue-specific mechanisms of glucocorticoid-responsive gene expression via HEXIM1

• Project/Area Number: 21790888
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Endocrinology
• Research Institution: The University of Tokyo
• Principal Investigator: SHIMIZU Noriaki The University of Tokyo, 医科学研究所, 特任研究員 (30396890)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: グルココルチコイド / 骨格筋 / ミオパチー / 筋萎縮 / ロコモティブシンドローム / ステロイド副作用 / 分岐鎖アミノ酸 / 栄養 / 遺伝子 / 発現制御 / 細胞・組織 / マイクロアレイ

Research Abstract

We identified that a mutually exclusive crosstalk between catabolic processes provoked by the adrenal glucocorticoid signal and anabolic processes conducted by nutrition sensing plays a central role in regulating skeletal muscle mass, establishing a molecular basis for developing a therapeutic approach for maintaining muscle mass. Our results suggest that this crosstalk underlies not only pathogenesis of steroid side effects including muscle atrophy but also maintenance of systemic energy homeostasis.

Research Products

• [Journal Article] Crosstalk between glucocorticoid receptor and nutritional sensor mTOR in skeletalmuscle. (2011)
  • Author(s): Shimizu N, Yoshikawa N, Ito N, Maruyama T, Suzuki Y, Takeda S, Nakae J, Tagata Y, Nishitani S, Takehana K, Sano M, Fukuda K,Suematsu M, Morimoto C, Tanaka H.
  • Journal Title: Cell Metab. 13(2) Pages: 170-182
  • Peer Reviewed
• [Journal Article] Crosstalk between glucocorticoid receptor and nutritional sensor mTOR in skeletal muscle (2011)
  • Author(s): Shimizu N, et al.
  • Journal Title: Cell Metabolism Volume: 13 Pages: 170-182
  • Peer Reviewed
• [Journal Article] Glucocorticoid protects rodent hearts from ischemia/reperfusion injury by activating lipocalin-type prostaglandin D synthase-derived PGD2 biosynthesis. (2009)
  • Author(s): Tokudome S, Sano M, Shinmura K, Matsuhayashi T, Morizane S, Moriyama H, Tamaki K, Hayashida K, Nakanishi H, Yoshikawa N, Shimizu N, Endo J, Katayama T, Murata M, Yuasa S, Kaneda R, Tomita K, Eguchi N, Urada Y, Asano K, Utsunomiya Y, Suzuki T, Taguchi R, Tanaka T, Fukuda K.
  • Journal Title: J Clin Invest. 119(6) Pages: 1477-1488
  • Peer Reviewed
• [Journal Article] Ligand-based gene expression profiling identifies critical role of glucocorticoid receptor in rat neonatal cardiomyocytes. (2009)
  • Author(s): Yoshikawa N, Nagasaki M, Sano M, Tokudome S, Ueno K, Shimizu N, Imoto S, Miyano S, Suematsu M, Fukuda K, Morimoto C, Tanaka H.
  • Journal Title: Am J Physiol Endocrinol Metab. 296(6)
  • Peer Reviewed
• [Journal Article] Glucocorticoid protects rodent hearts from ischemia/reperfusion injury by activating lipocalin-type prostaglandin D synthase-derived PGD2 biosynthesis (2009)
  • Author(s): Tokudome S, et al.
  • Journal Title: J Clin Invest 119 Pages: 1477-88
  • Peer Reviewed
• [Journal Article] Ligand-based gene expression profiling reveals novel roles of glucocorticoid receptor in cardiac metabolism (2009)
  • Author(s): Yoshikawa N, et al.
  • Journal Title: Am J Physiol Endocrinol Metab 296
  • Peer Reviewed
• [Presentation] グルココルチコイドによる転写因子KLF15 の骨格筋特異的発現活性化の意義 (2010)
  • Author(s): 清水宣明, 吉川賢忠, 丸山崇子, 竹鼻健司, 伊藤尚基, 武田伸一, 佐野元昭, 福田恵一, 森本幾夫, 田中廣壽
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] 心筋細胞におけるグルココルチコイド受容体の役割の解明 (2010)
  • Author(s): 丸山崇子, 吉川賢忠, 清水宣明, 佐野元昭, 福田恵一, 森本幾夫, 田中廣壽
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] グルココルチコイドによる転写因子KLF15の骨格筋特異的発現活性化の意義 (2010)
  • Author(s): 清水宣明, ほか
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートピアホテル ポートピアホール
  • Year and Date: 2010-12-07
• [Presentation] グルココルチコイド誘導性筋萎縮の分子機構の解明(1) (2010)
  • Author(s): 吉川賢忠, 清水宣明, 佐野元昭, 福田恵一, 森本幾夫, 田中廣壽
  • Organizer: 第18回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-11-27
• [Presentation] グルココルチコイド誘導性筋萎縮の分子機構の解明(2) (2010)
  • Author(s): 清水宣明, 吉川賢忠, 佐野元昭, 福田恵一, 森本幾夫, 田中廣壽
  • Organizer: 第18回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-11-27
• [Presentation] グルココルチコイド誘導性筋萎縮の分子機構の解明(2) (2010)
  • Author(s): 清水宣明, ほか
  • Organizer: 第18回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 名古屋WINK AICHI
  • Year and Date: 2010-11-27
• [Presentation] Crosstalk between glucocorticoid response and nutritional sensor in skeletal muscle. (2010)
  • Author(s): Shimizu N, Yoshikawa N, Ito N, Tagata Y, Takehana K, Maruyama T, Takeda S, Morimoto C, Tanaka H.
  • Organizer: Satellitesymposium "Nuclear Receptors" in ICE 2010
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-03-31
• [Presentation] Crosstalk between glucocorticoid response and nutritional sensor in skeletal muscle (2010)
  • Author(s): 清水宣明, et al.
  • Organizer: Satellite symposium "Nuclear Receptors" in ICE 2010
  • Place of Presentation: 京都
  • Year and Date: 2010-03-31
• [Presentation] The rolesof glucocorticoid receptor on cardiac metabolism. (2010)
  • Author(s): Yoshikawa N, Sano M, Tokudome S, Shimizu N, Nagasaki M, Imoto S, Miyano S, Fukuda K, Morimoto C, Tanaka H.
  • Organizer: 14th International Congress of Endocrinology.
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-03-29
• [Presentation] Crosstalk between glucocorticoid response and nutritional sensor in skeletal muscle. (2010)
  • Author(s): Shimizu N, Yoshikawa N, Ito N, Tagata Y, Takehana K, Maruyama T, Takeda S, Morimoto C, Tanaka H.
  • Organizer: 14th International Congress of Endocrinology.
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-03-29
• [Presentation] Crosstalk between glucocorticoid response and nutritional sensor in skeletal muscle (2010)
  • Author(s): 清水宣明, et al.
  • Organizer: 14th International Congress of Endocrinology(ICE 2010)
  • Place of Presentation: 京都
  • Year and Date: 2010-03-29
• [Presentation] グルココルチコイド受容体は心筋におけるアミノ酸代謝、プロスタグランジン産生を抑制する (2009)
  • Author(s): 吉川賢忠, 長崎正朗, 井本清哉, 宮野悟, 徳留さとり, 佐野元昭, 福田恵一, 清水宣明, 森本幾夫, 田中廣壽
  • Organizer: 第17回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2009-11-14
• [Presentation] in vivo におけるグルココルチコイド応答性遺伝子のHEXIM1 を介した発現制御 (2009)
  • Author(s): 清水宣明, 吉川賢忠, 丸山崇子, 森本幾夫, 田中廣壽
  • Organizer: 第17回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2009-11-14
• [Presentation] in vivo におけるグルココルチコイド応答性遺伝子のHEXIM1を介した発現制御 (2009)
  • Author(s): 清水宣明, ほか
  • Organizer: 第17回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2009-11-14
• [Presentation] HEXIM1 はグルココルチコイド受容体(GR)のhinge (D) 領域に結合してGR の転写活性を抑制する (2009)
  • Author(s): 吉川賢忠, 清水宣明, 森本幾夫, 田中廣壽
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 前橋
  • Year and Date: 2009-04-23
• [Presentation] グルココルチコイド(GC)応答性遺伝子発現のHEXIM1 による組織特異的制御機構 (2009)
  • Author(s): 清水宣明, 吉川賢忠, 森本幾夫, 田中廣壽
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 前橋
  • Year and Date: 2009-04-23
• [Presentation] グルココルチコイド(GC)応答性遺伝子発現のHEXIM1による組織特異的制御機構 (2009)
  • Author(s): 清水宣明, ほか
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 前橋
  • Year and Date: 2009-04-23
• [Remarks]
  • URL: http://first.lifesciencedb.jp/archives/2232