Elucidate the regulational mechanism of de-differentiation of cardiac myofibroblast in response to stretch

• Project/Area Number: 18K08084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Dokkyo Medical University
• Principal Investigator: Obi Syotaro 獨協医科大学, 医学部, 准教授 (10734452)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 伸展張力 / 線維芽細胞 / 脱分化 / 機械的刺激 / 線維化

Outline of Final Research Achievements

The proriferation level and migration level decreased after human cardiac myofibroblast were exposed to stretch. The protein expression level of fibrosis marker also decreased in response to stretch. It indicates that stretch induces de-differentiation of myofibroblast. Next the knockdown of TRPV4 which was an carcium ion channel in myofibroblast did not respond to stretch. These findings indicate that one of the cause of cardiac fibrosis is the decrease of stretch, the increase of TRPV4, and the increase of fibrosis.

Academic Significance and Societal Importance of the Research Achievements

心臓線維化の機序としてTRPV4が伸展張力に応答して線維化を制御していることが分かった。TRPV4をターゲットとした薬剤を開発することにより心臓の線維化を改善することができると期待できる。

Research Products

• [Journal Article] Allyl isothiocyanate (AITC) activates nonselective cation currents in human cardiac fibroblasts: possible involvement of TRPA1 (2021)
  • Author(s): Oguri Gaku、Nakajima Toshiaki、Kikuchi Hironobu、Obi Shotaro、Nakamura Fumitaka、Komuro Issei
  • Journal Title: Heliyon Volume: 7 Issue: 1 Pages: e05816-e05816
  • DOI: 10.1016/j.heliyon.2020.e05816
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Usefulness of New R-R Interval Analysis Using the Wearable Heart Rate Sensor WHS-1 to Identify Obstructive Sleep Apnea: OSA and RRI Analysis Using a Wearable Heartbeat Sensor (2020)
  • Author(s): Arikawa Takuo、Nakajima Toshiaki、Yazawa Hiroko、Kaneda Hiroyuki、Haruyama Akiko、Obi Syotaro、Amano Hirohisa、Sakuma Masashi、Toyoda Shigeru、Abe Shichiro、Tsutsumi Takeshi、Matsui Taishi、Nakata Akio、Shinozaki Ryo、Miyamoto Masayuki、Inoue Teruo
  • Journal Title: Journal of Clinical Medicine Volume: 9 Issue: 10 Pages: 3359-3359
  • DOI: 10.3390/jcm9103359
  • Peer Reviewed / Open Access
• [Journal Article] Short-term Safety and Mid-term Efficacy of Prasugrel Versus Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention (2019)
  • Author(s): Koyabu Y, Abe S, Sakuma M, Kanaya T, Obi S, Yoneda S, Toyoda S, Nakajima T, Inoue T.
  • Journal Title: Internal Medicine Volume: 58 Issue: 16 Pages: 2315-2322
  • DOI: 10.2169/internalmedicine.2262-18
  • NAID: 130007690129
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2019-08-15
  • Peer Reviewed / Open Access
• [Journal Article] Prediction of Acute-phase Complications in Patients with Infectious Endocarditis (2019)
  • Author(s): Saito F, Toyoda S, Arikawa T, Inami S, Watanabe R, Obi S, Sakuma M, Kanaya T, Abe S, Nakajima T, Inoue T.
  • Journal Title: Internal Medicine Volume: 58 Issue: 16 Pages: 2323-2331
  • DOI: 10.2169/internalmedicine.1813-18
  • NAID: 130007690141
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2019-08-15
  • Peer Reviewed / Open Access
• [Journal Article] Association of serum leptin and adiponectin concentrations with echocardiographic parameters and pathophysiological states in patients with cardiovascular disease receiving cardiovascular surgery. (2019)
  • Author(s): Sawaguchi T, Nakajima T, Haruyama A, Hasegawa T, Shibasaki I, Nakajima T, Kaneda H, Arikawa T, Obi S, Sakuma M, Ogawa H, Takei Y, Toyoda S, Nakamura F, Abe S, Fukuda H, Inoue T.
  • Journal Title: PLoS One Volume: 14(11) Issue: 11 Pages: e0225008-e0225008
  • DOI: 10.1371/journal.pone.0225008
  • Peer Reviewed / Open Access
• [Journal Article] Growth Differentiation Factor-15 (GDF-15) is a Biomarker of Muscle Wasting and Renal Dysfunction in Preoperative Cardiovascular Surgery Patients. (2019)
  • Author(s): Nakajima T, Shibasaki I, Sawaguchi T, Haruyama A, Kaneda H, Nakajima T, Hasegawa T, Arikawa T, Obi S, Sakuma M, Ogawa H, Toyoda S, Nakamura F, Abe S, Fukuda H, Inoue T.
  • Journal Title: J Clin Med Volume: 8(10) Issue: 10 Pages: 1576-1576
  • DOI: 10.3390/jcm8101576
  • Peer Reviewed / Open Access
• [Journal Article] Heat induces myogenic transcription factors of myoblast cells via transient receptor potential vanilloid 1 (Trpv1). (2018)
  • Author(s): Obi S, Nakajima T, Hasegawa T, Nakamura F, Sakuma M, Toyoda S, Tei C, and Inoue T.
  • Journal Title: FEBS Open Bio. Volume: 9(1) Issue: 1 Pages: 101-113
  • DOI: 10.1002/2211-5463.12550
  • Peer Reviewed / Open Access
• [Journal Article] Association of serum concentrations of irisin and the adipokines adiponectin and leptin with epicardial fat in cardiovascular surgery patients. (2018)
  • Author(s): Kaneda H, Nakajima T, Haruyama A, Shibasaki I, Hasegawa T, Sawaguchi T, Kuwata T, Obi S, Arikawa T, Sakuma M, Amano H, Toyoda S, Fukuda H, Inoue T.
  • Journal Title: PLoS One Volume: 13(8) Issue: 8 Pages: e0201499-e0201499
  • DOI: 10.1371/journal.pone.0201499
  • Peer Reviewed / Open Access
• [Journal Article] Muscle hypertrophy following blood flow-restricted low force isometric electrical stimulation in rat tibialis anterior: Role for muscle hypoxia. (2018)
  • Author(s): Nakajima T, Koide S, Yasuda T, Hasegawa T, Yamasoba T, Obi S, Toyoda S, Nakamura F, Inoue T, Poole DC, Kano Y
  • Journal Title: J Appl Physiol Volume: 印刷中 Issue: 1 Pages: 134-145
  • DOI: 10.1152/japplphysiol.00972.2017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mobilization of progenitor cells and assessment of vessel healing after second generation drug-eluting stenting by optical coherence tomography. (2018)
  • Author(s): Sakuma M, Nasuno T, Abe S, Obi S, Toyoda S, Taguchi I, Sohma R, Inoue K, Nishino S, Node K, Attizzani G, Bezerra H, Costa M, Simon D, and Inoue T.
  • Journal Title: Int J Cardiol Heart Vasc Volume: 18 Pages: 17-24
  • DOI: 10.1016/j.ijcha.2017.12.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 温熱刺激が骨格筋芽細胞を分化させるメカニズム (2021)
  • Author(s): 小尾正太郎
  • Organizer: 日本温泉気候物理医学会
  • Invited
• [Presentation] 骨格筋芽細胞はHSP70を介して蛋白合成系を増大する (2020)
  • Author(s): 小尾正太郎、井上晃男、中島敏明
  • Organizer: 日本心臓リハビリテーション学会
• [Presentation] Trpv1 senses hyperthermia following differentiation in myoblast cells. (2020)
  • Author(s): Syotaro Obi, Teruo Inoue, Toshiaki Nakajima.
  • Organizer: 日本循環器学会
• [Presentation] 温熱刺激による骨格筋分化の機序 (2020)
  • Author(s): 小尾正太郎
  • Organizer: 第11回ハートクラブカンファレンス