Elucidation of roles played by MRTF-A, a rho-dependent transcriptional co-activator, in pathological cardiac remodeling

• Project/Area Number: 21790719
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto University
• Principal Investigator: USAMI Satoru Kyoto University, 医学研究科, 医員 (30521752)
• 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: 心筋リモデリング / 遺伝子転写調節 / アンジオテンシンII

Research Abstract

In this study, we evaluated roles played by myocardin-related transcription factor-A (MRTF-A), a co-activator of serum response factor (SRF), in pathological cardiac remodeling. Mechanical stress and neurohumoral stimulation onto cardiac myocytes induced nuclear translocation of MRTF-A, a co-activator of serum response factor (SRF) in a Rho and actin dynamics-dependent manner, thereby activating SRF. Our findings define the Rho- and actin dynamics-dependent nuclear translocation of MRTF-A as a novel common signaling mechanism underlying both mechanical stretch- and neurohumoral stimulation-induced cardiac hypertrophy and fetal gene activation during pathological cardiac remodeling.

Research Products

• [Journal Article] Zinc-finger protein 90 negatively regulates neuron-restrictive silencer factor-mediated transcriptional repression of fetal cardiac genes (2011)
  • Author(s): Hata L, Murakami M, Kuwahara K, Nakagawa Y, Kinoshita H, Usami S, Yasuno S, Fujiwara M, Kuwabara Y, Minami T, Yamada Y, Yamada Y, Nakao K, Ueshima K, Nishikimi T, Nakao K
  • Journal Title: J Mol Cell Cardiol. (in press)
  • Peer Reviewed
• [Journal Article] Zinc-finger protein 90 negatively regulates neuron-restrictive silencer factor-mediated transcriptional repression of fetal cardiac genes. (2011)
  • Author(s): Hata L, Murakami M, Usami S, 他13名
  • Journal Title: Journal of Molecular and Cellular Cardiology Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] MRTF-A is a common mediator of mechanical stress- and neurohumoral stimulation-induced cardiac hypertrophic signaling leading to activation of BNP gene expression (2010)
  • Author(s): Kuwahara K, Kinoshita H, Kuwabara Y, Nakagawa Y, Usami S, Minami T, Yamada Y, Fujiwara M, Nakao K
  • Journal Title: Mol Cell Biol 30(17) Pages: 4134-4148
  • Peer Reviewed
• [Journal Article] Inhibition of TRPC6 Channel Activity Contributes to the Anti-hypertrophic Effects of Natriuretic Peptides-Guanylyl Cyclase-A Signaling in the Heart (2010)
  • Author(s): Kinoshita H, Kuwahara K, Nishida M, Jiang Z, Rong X, Kiyonaka S, Kuwabara Y, Kurose H, Inoue R, Mori Y, Li Y, Nakagawa Y, Usami S, Fujiwara M, Yamada Y, Minami T, Ueshima K, Nakao K
  • Journal Title: Circ Res 106(12) Pages: 1849-1860
  • Peer Reviewed
• [Journal Article] MRTF-A is a common mediator of mechanical stress- and neurohumoral stimulation-induced cardiac hypertrophic signaling leading to activation of BNP gene expression (2010)
  • Author(s): Kuwahara K, Usami S, 他7名
  • Journal Title: Molecular and Cellular Biology Volume: 30 Pages: 4134-4148
  • Peer Reviewed
• [Journal Article] Inhibition of TRPC6 Channel Activity Contributes to the Anti-hypertrophic Effects of Natriuretic Peptides-Guanylyl Cyclase-A Signaling in the Heart (2010)
  • Author(s): Kinoshita H, Usami S, 他16名
  • Journal Title: Circulation Research Volume: 106 Pages: 1849-1860
  • Peer Reviewed
• [Journal Article] p300 plays a critical role in maintaining cardiac mitochondrial function and cell survival in postnatal hearts (2009)
  • Author(s): Nakagawa Y, Kuwahara K, Takemura G, Akao M, Kato M, Arai Y, Takano M, Harada M, Murakami M, Nakanishi M, Usami S, Yasuno S, Kinoshita H, Fujiwara M, Ueshima K, Nakao K
  • Journal Title: Circ.Res. 105(8) Pages: 746-754
  • Peer Reviewed
• [Journal Article] Endogenous cardiac natriuretic peptides protect the heart in a mouse model of dilated cardiomyopathy and sudden death (2009)
  • Author(s): Yasuno S, Usami S, Kuwahara K, Nakanishi M, Arai Y, Kinoshita H, Nakagawa Y, Fujiwara M, Murakami M, Ueshima K, Harada M, Nakao K
  • Journal Title: Am J Physiol Heart Circ Physiol 296(6) Pages: 1804-1810
  • Peer Reviewed
• [Journal Article] p300 plays a critical role in maintaining cardiac mitochondrial function and cell survival in postnatal hearts (2009)
  • Author(s): Nakagawa Y, Usami S, 他14名
  • Journal Title: Circulation Research 105 Pages: 746-754
  • Peer Reviewed
• [Journal Article] The cardiac pacemaker-specific channel Hcn4 is a direct transcriptional target of MEF2 (2009)
  • Author(s): Yasuno S, Usami S, 他10名
  • Journal Title: American Journal of Physiology, Heart and Circulatory Physiology 296
  • Peer Reviewed
• [Journal Article] Prognostic value of myocardial perfusion SPECT images in combination with the maximal heart rate at exercise testing in Japanese patients with suspected ischemic heart disease : a sub-analysis of J-ACCESS. (2009)
  • Author(s): Ueshima K, Usami S, 他6名
  • Journal Title: Annals of Nuclear Medicine 23 Pages: 849-854
  • NAID: 10026099641
  • Peer Reviewed
• [Presentation] Blockade of TRPC6 is a novel therapeutic approach against pathological cardiac remodeling (2010)
  • Author(s): Hideyuki Kinoshita, Usami Satoru, 他8名
  • Organizer: 第14回 日本心不全学会 学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-10-07
• [Presentation] Rho and actin dynamics-dependent nuclear translocation of MRTF-A is a common molecular mechanisms underlying both mechanical stretchand neurohumoral stimulation-induced cardiac hypertrophy (2010)
  • Author(s): Koichiro Kuwahara, Satoru Usami, 他7名。
  • Organizer: 14th Annual Scientific Session of the Society of Cardiovacular Endocrinology and Metabolism
  • Place of Presentation: Nara
  • Year and Date: 2010-04-01
• [Presentation] Rho and actin dynamics-dependent nuclear translocation of MRTF-A is a common molecular mechanisms underlying both mechanical stretch- and neurohumoral stimulation-induced cardiac hypertrophy (2010)
  • Author(s): Koichiro Kuwahara, Satoru Usami, 他7名
  • Organizer: 14th Annual Scientific Session of the Society of Cardiovacular Endocrinology and Metabolism March
  • Place of Presentation: Nara, Japan
  • Year and Date: 2010-04-01
• [Presentation] Natriuretic Peptides-Guanylyl Cyclase-A Signaling Pathway Inhibits TRPC6-Mediated Pro-Hypertrophic Signaling in the Hearts (2010)
  • Author(s): Hideyuki Kinoshita, Satoru Usami, 他11名
  • Organizer: 14th Annual Scientific Session of the Society of Cardiovacular Endocrinology and Metabolism March
  • Place of Presentation: Nara, Japan
  • Year and Date: 2010-04-01
• [Presentation] CT dinucleotide repeat polymorphism in the promoter region of Guanylyl Cyclase-A gene is associated with essential hypertension in the Japanese. (2010)
  • Author(s): Satoru Usami, et al.
  • Organizer: 14th International Congress of Endocrinology.
  • Place of Presentation: Kyoto
  • Year and Date: 2010-03-29
• [Presentation] CT dinucleotide repeat polymorphism in the promoter region of Guanylyl Cyclase-A gene is associated with essential hypertension in the Japanese (2010)
  • Author(s): 宇佐美覚
  • Organizer: 14th International Congress of Endocrinology
  • Place of Presentation: 京都国際会議場、京都
  • Year and Date: 2010-03-29
• [Presentation] ナトリウム利尿ペプチドの心保護作用におけるTRPC6の役割 (2009)
  • Author(s): 木下秀之、桑原宏一郎、井上隆司、西田基宏、黒瀬等、清中茂樹、森泰生、榮向路、李育浩、村上政男,中川靖章、保野慎治, 宇佐美覚,藤原正隆,桑原佳宏,山田優子、南丈史,原田昌樹、上嶋健, 中尾一和
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 群馬、前橋。
• [Remarks] ホームページ等
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/jpn/research/cardio.html
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/jpn/research/cardio.html
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  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/jpn/research/cardio.html