Investigation of the significance of MRTF-A, a co-activator of SRF, in the development of obesity that is an underlying risk factor for cardiovascular diseases

• Project/Area Number: 16K15442
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Shinshu University
• Principal Investigator: KUWAHARA KOICHIRO 信州大学, 学術研究院医学系, 教授 (30402887)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 分子心臓学 / 転写因子 / シグナル伝達 / 糖代謝 / 肥満 / 脂肪分化 / 分子心臓病学 / 転写調節 / メタボリックシンドローム

Outline of Final Research Achievements

Metabolic syndrome derived from central obesity and fat accumulation underlies the development of cardiovascular disease. Detailed molecular mechanisms leading to central obesity and fat accumulation remains unresolved. Recently, our study group found that MRTF-A, Rho-dependent transcriptional coactivator of SRF, plays a significant role in the regulation of adipocyte proliferation, fat accumulation and glucose metabolism by analyzing MRTF-A knockout mice. In this study, we investigated the precise molecular mechanisms and potential clinical relevance of MRTF-A in adipocyte differentiation and fat accumulation that lead to the development of metabolic syndrome and obesity

Research Products

• [Int'l Joint Research] Michigan State University/University of Texas(米国)
• [Int'l Joint Research] Academic Medical Center(Netherlands)
• [Int'l Joint Research] University of Texas/Michigan State Unversity(米国)
• [Journal Article] Rats deficient C-type natriuretic peptide suffer from impaired skeletal growth without early death. (2018)
  • Author(s): Fujii T, Hirota K, Yasoda A, Takizawa A, Morozumi N, Nakamura R, Yotsumoto T, Kondo E, Yamashita Y, Sakane Y, Kanai Y, Ueda Y, Yamauchi I, Yamanaka S, Nakao K, Kuwahara K, Jindo T, Furuya M, Mashimo T, Inagaki N, Serikawa T, Nakao K.
  • Journal Title: PROS ONE Volume: 13 Issue: 3 Pages: e0194812-e0194812
  • DOI: 10.1371/journal.pone.0194812
  • NAID: 120006466606
  • Peer Reviewed / Open Access
• [Journal Article] Macro-pro-B-type natriuretic peptide (proBNP) and hidden macro-N-terminal proBNP:Case report. (2017)
  • Author(s): Nakagawa Y, Nishikimi T, Sakai H, Ohno S, Kinoshita H, Inazumi H, Moriuchi K, Kuwahara K, Horie M, Kimura T.
  • Journal Title: Clinical Biochemistry Volume: 52 Pages: 148-152
  • DOI: 10.1016/j.clinbiochem.2017.10.019
  • Peer Reviewed
• [Journal Article] Impact of extracellular matrix on engraftment and maturation of pluripotent stem cell-derived cardiomyocytes in a rat myocardial infarct model. (2017)
  • Author(s): Ogasawara T, Okano S, Ichimura H, Kadota S, Tanaka Y, Minami I, Uesugi M, Wada Y, Saito N, Okada K, Kuwahara K, Shiba Y
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 8630-8630
  • DOI: 10.1038/s41598-017-09217-x
  • Peer Reviewed / Open Access
• [Journal Article] Kyoto Congestive Heart Failure (KCHF) Study: Rationale and Design (2017)
  • Author(s): Yamamoto E, Kato T, Ozasa N, Yaku H, Inuzuka Y, Tamaki Y, Kitai T, Morimoto T, Taniguchi R, Iguchi M, Kato M, Takahashi M, Jinnai T, Ikeda T, Nagao K, Kawai T, Komasa A,Nishikawa R, Kawase Y, Morinaga T,Kawashima T, Motohashi Y, Kawato M, Toyofuku M, Sato Y, Kuwahara K, et al.
  • Journal Title: ESC Heart Fail Volume: 4 Issue: 3 Pages: 216-223
  • DOI: 10.1002/ehf2.12138
  • NAID: 120007100124
  • Peer Reviewed / Open Access
• [Journal Article] Impressive predictive value of ankle-brachial index for very long-term outcomes in patients with cardiovascular disease: IMPACT-ABI study. (2017)
  • Author(s): Miura T, Minamisawa M, Ueki Y, Abe N, Nishimura H, Hashizume N, Mochidome T, Harada M, Oguchi Y, Yoshie K, Shoin W, Saigusa T, Ebisawa S, Motoki H, Koyama J, Ikeda U, Kuwahara K.
  • Journal Title: PLoS One Volume: 12 Issue: 6 Pages: e0177609-e0177609
  • DOI: 10.1371/journal.pone.0177609
  • Peer Reviewed / Open Access
• [Journal Article] B-Type Natriuretic Peptide in Heart Failure With Preserved Ejection Fraction ― Relevance to Age-Related Left Ventricular Modeling in Japanese ― (2017)
  • Author(s): Tanabe N, Ikeda S, Tahara N, Fukuda K, Hatano M, Ito H, Nakayama T, Anzai T, Hashimoto A, Inoue T, Kajinami K, Kihara Y, Kinoshita H, Kuwahara K, Murohara T, Okazaki O, Sakai S, Satoh T, Takeda Y, Takeishi Y, Taniguchi M, Watanabe H, Yamamoto T, Yamauchi-Takihara K, Yoshioka K, Sasayama S.
  • Journal Title: Circulation Journal Volume: 81 Issue: 7 Pages: 1006-1013
  • DOI: 10.1253/circj.CJ-16-1282
  • NAID: 130006887044
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] MiR30-GALNT1/2 Axis-Mediated Glycosylation Contributes to the Increased Secretion of Inactive Human Prohormone for Brain Natriuretic Peptide (proBNP) From Failing Hearts. (2017)
  • Author(s): Nakagawa Y, Nishikimi T, Kuwahara K, Fujishima A, Oka S, Tsutamoto T, Kinoshita H, Nakao K, Cho K, Inazumi H, Okamoto H, Nishida M, Kato T, Fukushima H, Yamashita JK, Wijnen WJ, Creemers EE, Kangawa K, Minamino N, Nakao K, Kimura T.
  • Journal Title: J Am Heart Assoc. Volume: 6 Issue: 2
  • DOI: 10.1161/jaha.116.003601
  • NAID: 120007100125
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Endothelium-derived C-type natriuretic peptide contributes to blood pressure regulation by maintaining endothelial integrity. (2017)
  • Author(s): Nakao K, Kuwahara K, Nishikimi T, Nakagawa Y, Kinoshita H, Minami T, Kuwabara Y, Yamada C, Yamada Y, Tokudome T, Nagai-Okatani C, Minamino N, Nakao YM, Yasuno S, Ueshima K, Sone M, Kimura T, Kangawa K, Nakao K
  • Journal Title: Hypertension. Volume: 69 Issue: 2 Pages: 286-296
  • DOI: 10.1161/hypertensionaha.116.08219
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Diagnostic advantage of stress computed tomography myocardial perfusion over single-photon emission computed tomography for the assessment of myocardial ischemia. (2017)
  • Author(s): Ueki Y, Izawa A, Kashiwagi D, Nishiyama S, Aso S, Suzuki C, Sakurai S, Oguchi K, Yazaki Y, Ikeda U, Kuwahara K.
  • Journal Title: J Cardiol Volume: 印刷中 Issue: 2 Pages: 147-154
  • DOI: 10.1016/j.jjcc.2016.11.004
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Increase of Total Nephron Albumin Filtration and Reabsorption in Diabetic Nephropathy. (2017)
  • Author(s): Mori KP, Yokoi H, Kasahara M, Imamaki H, Ishii A, Kuwabara T, Koga K, Kato Y, Toda N, Ohno S, Kuwahara K, Endo T, Nakao K, Yanagita M, Mukoyama M, Mori K.
  • Journal Title: J Am Soc Nephrol. Volume: 28 Issue: 1 Pages: 278-289
  • DOI: 10.1681/asn.2015101168
  • NAID: 120005820888
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TRPC3-GEF-H1 axis mediates pressure overload-induced cardiac fibrosis. (2016)
  • Author(s): Numaga-Tomita T., Kitajima N., Kuroda T., Nishimura A., Miyano K., Yasuda S., Kuwahara K., Sato Y., Ide T., Birnbaumer L., Sumimoto H., Mori Y. and Nishida M.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 39383-39383
  • DOI: 10.1038/srep39383
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Clinical Characteristics and Outcomes of Patients with High Ankle-Brachial Index from the IMPACT-ABI Study (2016)
  • Author(s): Nishimura H, Miura T, Minamisawa M, Ueki Y, Abe N, Hashizume N, Mochidome T, Harada M, Shimizu K, Shoin W, Yoshie K, Oguchi Y, Ebisawa S, Motoki H, Izawa A, Koyama J, Ikeda U, Kuwahara K.
  • Journal Title: PLoS One Volume: 11 Issue: 11 Pages: 1-12
  • DOI: 10.1371/journal.pone.0167150
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Brain Natriuretic Peptide Counteracting the Renin-angiotensin-aldosterone System in Accelerated Malignant Hypertension (2016)
  • Author(s): Nakagawa H, Mizuno Y, Harada E, Morikawa Y, Kuwahara K, Saito Y, Yasue H
  • Journal Title: Am J Med Sci Volume: 352 Issue: 5 Pages: 534-539
  • DOI: 10.1016/j.amjms.2016.08.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling. (2016)
  • Author(s): Kitajima N., Numaga-Tomita T., Watanabe M., Kuroda T., Nishimura A., Miyano K., Yasuda S., Kuwahara K., Sato Y., Ide T., Birnbaumer L., Sumimoto H., Mori Y. and Nishida M
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 37701-37701
  • DOI: 10.1038/srep37001
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Prevention of abdominal aortic aneurysm progression by oral administration of green tea polyphenol in a rat model. (2016)
  • Author(s): Setozaki S, Minakata K, Masumoto H, Hirao S, Yamazaki K, Kuwahara K, Ikeda T, Sakata R.
  • Journal Title: J Thorac Cardiovasc Surg. Volume: - Issue: 6 Pages: 1803-1812
  • DOI: 10.1016/j.jvs.2016.06.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Ablation of the N-type calcium channel ameliorates diabetic nephropathy with improved glycemic control and reduced blood pressure. (2016)
  • Author(s): Ohno S, Yokoi H, Mori K, Kasahara M, Kuwahara K, Fujikura J, Naito M, Kuwabara T, Imamaki H, Ishii A, Saleem MA, Numata T, Mori Y, Nakao K, Yanagita M, Mukoyama M
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 27192-27192
  • DOI: 10.1038/srep27192
  • NAID: 120007100128
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Transcriptional pathways underling the development of heart failure (2018)
  • Author(s): 桑原宏一郎
  • Organizer: 第82回日本循環器学会学術集会
• [Presentation] Endothelium-derived C-type natriuretic peptide regulates blood pressure through the maintenance of endothelial function (2017)
  • Author(s): Kuwahara K, Nakao K, Nishikimi T, Nakagawa Y, Kinoshita H, Tokudome T, Minamino N, Kimura T, Kangawa K, Nakao K
  • Organizer: Heart Failure 2017
  • Int'l Joint Research
• [Presentation] Endothelial dysfunction underlies blood pressure elevation in endothelium-specific C-type natriuretic peptide knockout mice. (2017)
  • Author(s): Kuwahara K, Nakao K, Nishikimi T, nakagawa Y, Tokudome T, Minamino N, Kimura T, Kangawa K, Nakao K
  • Organizer: ESC Congress 2017
  • Int'l Joint Research
• [Presentation] Alternative subcutaneous implantable cardioverter defibrillator lead placement in adult patients with complex congenital heart disease (2017)
  • Author(s): Oguchi Y, Shoda M, Kobayasshi H, Shoin W, Okano T, Takeuchi T, Okada A, Motoki H, Kuwahara K
  • Organizer: Heart Rhythm 2017
  • Int'l Joint Research
• [Presentation] 2-year natural history of lower limbs in patients with end-stage renal disease on hemodialysis due to diabetic nephropathy; from PREDICT study. (2017)
  • Author(s): Kato T, Miyashita Y, Miura T, Kanno Y, Sone H, Tokoo M, Ako S, Mizukami E, Terashima M, Yokota D, Nakagawa M, Fujimori Y, Higuchi M, Mochidome T, Sakai T, Senda K, Oguchi Y, Yamasaki S, Saigusa T, Ebisawa S, Okada A, Motoki H, Kuwahara K
  • Organizer: Transcatheter Cardiovascular Therapeutics (TCT) 2017
  • Int'l Joint Research
• [Presentation] Development and Validation of a Novel Scoring System for Predicting Chronic Outcome After Percutaneous Coronary Intervention for Coronary Chronic Total Occlusion (2017)
  • Author(s): Ebisawa S, Kosaka S, Yamane M, Muramatsu T, Okamura A, Kashima Y, Matsuno S, Sakurada M, Kijima M, Tanabe M, Habara M, Kuwahara K.
  • Organizer: AHA2017
  • Int'l Joint Research
• [Presentation] Validation of a Prognostic Risk Score for Major Bleeding Events in Patients Undergoing Percutaneous Coronary Intervention: From the SHINANO Registry. (2017)
  • Author(s): Senda K, Miura T, Mochidome T, Sakai T, Minamisawa M, Kato T, Saigusa T, Ebisawa S, Motoki H, Kuwahara K.
  • Organizer: AHA2017
  • Int'l Joint Research
• [Presentation] Secretion of proBNP is regulated by MiR30-GALNTs axis dependent O-linked glycosylation in the pathological myocardium (2016)
  • Author(s): Nakagawa Y, Nishikimi T, Kuwahara K, Kinoshita H, Inazumi H, Moriuchi K, Kato T, Minamino N, Nakao K, Kimura T
  • Organizer: AHA Scientific Session 2016
  • Place of Presentation: New Orleans, Louisiana, USA
  • Year and Date: 2016-11-13
  • Int'l Joint Research
• [Presentation] MiR30-GALNT1/2 axis-mediatede glycosylation regulates the increase in inactive human pro-BNP secretion from failing heart. (2016)
  • Author(s): Kuwahara K, Nakagawa Y, Nishikimi T, Kinoshita H, Okamoto H, Kato T, Kangawa K, Minamino N, Nakao K, Kimura T
  • Organizer: Hypertension Seoul 2016, The 26th Scientific meeting of the International Society of Hypertension
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2016-09-24
  • Int'l Joint Research
• [Presentation] Unprocessed proBNP secretion is regulated by MiR30-GALNTs axis dependent O-glycosylation in the pathological myocardium.. (2016)
  • Author(s): Nakagawa Y, Nishikimi T, Kuwahara K, Kinoshita H, Yamada C, Inazumi H, Nakao K, Kimura T
  • Organizer: AHA BCVS2016
  • Place of Presentation: Arizona, USA
  • Year and Date: 2016-07-18
  • Int'l Joint Research
• [Presentation] MiR30-GALNT1/2 axis-mediated glycosylation at threonine 48 and 71 plays an essential role in the increased secretion of unprocessed pro-brain natriuretic peptide by failing hearts (2016)
  • Author(s): Kuwahara K, Nakagawa Y, Nishikimi T, Kangawa K, Minamino N, Nakao K, Kimura T.
  • Organizer: Heart Failure 2016
  • Place of Presentation: Florence, Italy
  • Year and Date: 2016-05-21
  • Int'l Joint Research
• [Presentation] MiR30-GALNTs axis-mediated O-glycosylation plays an important role in the increased secretion of unprocessed pro-brain natriuretic peptide by failing heart (2016)
  • Author(s): Nakagawa Y, Nishikimi T, Kuwahara K, Nakao K and Kimura T
  • Organizer: Keystone symposia
  • Place of Presentation: Utah, USA
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Book] Endocrinology of the Heart in Health and Disease. (2016)
  • Author(s): Nishikimi T, Kuwahara K, Nakagawa Y, Kangawa K, and Nakao K
  • Total Pages: 378
  • Publisher: Elsevier Scinence
• [Remarks] 信州大学医学部循環器内科
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/department/doctor/zouki/i-oreg/cardiovascular/
• [Remarks] 信州大学 循環器内科学教室
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/department/doctor/zouki/i-oreg/cardiovascular/