Establishment and application of the new treatment method of evaluation method of pressure ulcers, diabetic skin ulcers by secreted miRNA

• Project/Area Number: 25460217
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Asahikawa Medical College (2014-2015); Nagoya City University (2013)
• Principal Investigator: Fujii Satoshi 旭川医科大学, 医学部, 教授 (90291228)
• Co-Investigator(Kenkyū-buntansha): OZEKI Tetsuya 名古屋市立大学, 薬学研究科, 教授 (60277259) ; ISOGAI Zenzou 独立行政法人国立長寿医療研究センター, その他部局, その他 (20285208) ; IWAKI Soichiro 名古屋市立大学, 薬学研究科, 講師 (60399962)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 高齢者 / 皮膚潰瘍 / 褥瘡 / 糖尿病 / 分泌型miRNA / バイオマーカー

Outline of Final Research Achievements

There was abundant matrix metalloprotease (MMP)-9 in exudate obtained from chronic wounds such as from elderly or diabetes mellitus. Excessive MMP-9 may delay wound healing and correlate with clinical severity. Ointment base has been considered to have no pharmacologic actions. However, in this study macrogol, an ointment base, exhibited pharmacologic activity to reduce MMP-9 activity. The concentration of microRNA, miR-126, varied greatly depending on the characteristics of would exudate. The effect of hypoxia on endothelial miRNA and function was evaluated using in vitro cell culture system. Knockdown and overexpression of miR-126 were involved in the regulation of MMP-9 in endothelial cells. The results suggested that miR-126 in chronic wound exudates may be involved in angiogenesis and blood flow, affecting the recovery of chronic wounds. The study may provide platform to develop new strategies of therapy against chronic wounds typically seen in elderly or diabetic patients.

Research Products

• [Journal Article] Targeting ceramide synthase 6-dependent metastasis-prone phenotype in lung cancer cells. (2016)
  • Author(s): Suzuki M, et al.
  • Journal Title: J. Clin. Invest. Volume: 126 Issue: 1 Pages: 254-265
  • DOI: 10.1172/jci79775
  • Peer Reviewed / Open Access
• [Journal Article] PAI-1 in Myocardial Remodeling: Is Pharmacological Suppression by ARB Beneficial? (2016)
  • Author(s): Satoshi Fujii.
  • Journal Title: J Atheroscler Thromb Volume: 23 Issue: 5 Pages: 550-551
  • DOI: 10.5551/jat.ed030
  • NAID: 130005149013
  • Peer Reviewed / Open Access
• [Journal Article] Serotonin in Peripheral Blood Reflects Oxidative Stress and Plays a Crucial Role in Atherosclerosis: Novel Insights toward Holistic Anti-atherothrombotic Strategy. (2016)
  • Author(s): Sugiura T, Yamashita S, Hirowatari Y, Fujii S, Ohte N.
  • Journal Title: Atherosclerosis Volume: 246 Pages: 157-160
  • DOI: 10.1016/j.atherosclerosis.2016.01.015
  • Peer Reviewed
• [Journal Article] Accurate quantitative measurements of brachial artery cross-sectional vascular area and vascular volume elastic modulus using automated oscillometric measurements - comparison with brachial artery ultrasound. (2015)
  • Author(s): Yuuki Tomiyama, Keiichiro Yoshinaga, Satoshi Fujii, Noriki Ochi, Mamiko Inoue, Mutumi Nishida, Kumi Aziki, Hideo Nishibayashi, Tatsunori Horie, Chietsugu Katoh, Nagara Tamaki.
  • Journal Title: Hypertens Res Volume: 38 Pages: 478-484
  • Peer Reviewed / Open Access
• [Journal Article] Circulating level of microRNA-126 may be a potential biomarker for recovery from smoking-related vascular damage in middle-aged habitual smokers. (2015)
  • Author(s): Sugiura T, Dohi Y, Yamashita S, Iwaki S, Ito S, Sanagawa A, Ohte N, Fujii S.
  • Journal Title: Int J Cardiol: Heart and Vasculature Volume: 7 Pages: 83-87
  • Peer Reviewed
• [Journal Article] The relationship between repolarization parameters and serum electrolyte levels in patients with J wave syndromes. (2015)
  • Author(s): Nobuyuki Sato, Rie Sasaki, Marina Imahashi, Eisuke Ito, Kumiko Saito, Haruyo Kubota, Ahmed Karim Talib, Naka Sakamoto, Kazumi Akasaka, Yasuaki Saijo, Yuichiro Kawamura, Satoshi Fujii, Naoyuki Hasebe.
  • Journal Title: Magnesium Research Volume: 28 Issue: 1 Pages: 1-13
  • DOI: 10.1684/mrh.2015.0379
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive Assessment of Impaired Peripheral and Coronary Artery Endothelial Function in Smokers Using Brachial Artery Ultrasound and Oxygen-15-labeled Water PET (2015)
  • Author(s): Noriki Ochi, Keiichiro Yoshinaga,Yoichi M. Ito, Yuuki Tomiyama, Mamiko Inoue, Mutsumi Nishida, Osamu Manabe, Hitoshi Shibuya , Chikara Shimizu, Eriko Suzuki, Satoshi Fujii, Chietsugu Katoh, Nagara Tamaki.
  • Journal Title: Journal of Cardiology Volume: in press Issue: 4 Pages: 316-323
  • DOI: 10.1016/j.jjcc.2015.10.006
  • Peer Reviewed / Open Access
• [Journal Article] 動脈硬化性疾患と慢性炎症、血栓症：臨床検査の視点から (2015)
  • Author(s): 藤井 聡
  • Journal Title: 臨床病理 Volume: 63 Pages: 605-611
  • Peer Reviewed
• [Journal Article] Elevated right ventricular oxidative metabolism evaluated using C-11 acetate PET in patients with pulmonary hypertension. (2014)
  • Author(s): Yoshinaga K, Ohira H, Tsujino I, Katoh C, Kasai K, Manabe O, Sato T, Oyama-Manabe N, Fujii S, Ito Y, Nishimura M, Tamaki N.
  • Journal Title: European Journal of Nuclear Medicine and Molecular Imaging Volume: 41 Pages: 1240-1250
  • Peer Reviewed
• [Journal Article] TNF-α production in NKT cell hybridoma is regulated by sphingosine-1-phosphate: implications for inflammation in atherosclerosis. (2014)
  • Author(s): Ito S, Iwaki S, Kondo R, Satoh M, Iwabuchi K, Ohkawa R, Mishima Y, Yatomi Y, Furumoto T, Tsutsui H, Fujii S.
  • Journal Title: Coronary Artery Disease Volume: 25 Pages: 311-320
  • Peer Reviewed
• [Journal Article] Resolution of left atrial thrombus with novel oral anticoagulants. (2014)
  • Author(s): Fujii S
  • Journal Title: J Cardiol Cases Volume: 10 Pages: 241-242
  • Peer Reviewed
• [Journal Article] miRNA (マイクロRNA, microRNA) (2014)
  • Author(s): 藤井 聡
  • Journal Title: 日本臨床 別冊 臨床高血圧学 Volume: 72 Pages: 218-221
• [Journal Article] 医師・薬剤師・看護師による褥瘡チーム医療の経済的側面に関する考察 (2013)
  • Author(s): 古田 勝経，溝神 文博，宮川 哲也，森川 拓，永田 治，永田 実，福澤 悦子，油座 マミ，櫻井 淳二，庄司 理恵，藤井 聡
  • Journal Title: 日本病院・医療管理学会誌 Volume: 50 Pages: 15-23
  • NAID: 10031187644
  • Peer Reviewed
• [Journal Article] Natural killer T cells are required for lipopolysaccharide-mediated enhancement of atherosclerosis in apolipoprotein E-deficient mice (2013)
  • Author(s): Andoh Y, Ogura H, Satoh M, Shimano K, Okuno H, Fujii S, Ishimori N, Eshima K, Tamauchi H, Otani T, Nakai Y, Van Kaer L, Tsutsui H, Onoe K, Iwabuchi K
  • Journal Title: Immunobiology Volume: 218 Issue: 4 Pages: 561-569
  • DOI: 10.1016/j.imbio.2012.07.022
  • Peer Reviewed
• [Journal Article] Cigarette Smoking Induces Vascular Damage and Persistent Elevation of Plasma Serotonin Unresponsive to 8 Weeks of Smoking Cessation. (2013)
  • Author(s): Sugiura T, Dohi Y, Hirowatari Y, Yamashita S, Ohte N, Kimura G, Fujii S.
  • Journal Title: Int J Cardiol Volume: 166 Issue: 3 Pages: 748-749
  • DOI: 10.1016/j.ijcard.2012.09.173
  • Peer Reviewed
• [Journal Article] Physicochemical characterization of tretinoin tocoferil emulsion and povidone-iodine sugar ointment blend developed for improved regulation of wound moisture. (2013)
  • Author(s): Noda Y, Saito M, Watanabe K, Sanagawa A, Sobajima Y, Fujii S.
  • Journal Title: Chem Pharm Bull Volume: 61 Pages: 700-705
  • NAID: 130003360805
  • Peer Reviewed
• [Journal Article] Staphylococcal superantigen-like protein 10 (SSL10) inhibits blood coagulation by binding to prothrombin and factor Xa via theirγ-carboxyglutamic acid (Gla) domain (2013)
  • Author(s): Itoh S, Yokoyama R, Kamoshida G, Fujiwara T, Okada H, Takii T, Tsuji T, Fujii S, Hashizume H, Onozaki K
  • Journal Title: J Biol Chem Volume: 288 Issue: 30 Pages: 21569-21580
  • DOI: 10.1074/jbc.m113.451419
  • Peer Reviewed
• [Journal Article] Increased Plasma Sphingosine-1-Phosphate in Obese Subjects and Its Capacity to Increase Expression of Plasminogen Activator Inhibitor-1 in Adipocytes (2013)
  • Author(s): Shiori Ito, Soichiro Iwaki, Keiko Koike, Yuichiro Yuda, Ayako Nagasaki, Ryunosuke Ohkawa, Yutaka Yatomi, Tomoo Furumoto, Hiroyuki Tsutsui, Burton E Sobel, Satoshi Fujii
  • Journal Title: Coron. Artery Dis Volume: 24 Issue: 8 Pages: 642-650
  • DOI: 10.1097/mca.0000000000000033
  • Peer Reviewed
• [Presentation] 側鎖にアリル基を持つPEOを用いた新規軟膏基剤の開発． (2016)
  • Author(s): 浅井大知、山下啓司、藤井 聡、野田康弘．
  • Organizer: 第35回褥瘡研究会
  • Place of Presentation: 名古屋
  • Year and Date: 2016-02-02
• [Presentation] Altered Vascular Elasticity Reflected Vascular Endothelial Dysfunction and Elevated Galectin-3 Using Novel Brachial Artery Vascular Volume Elastic Modulus With Automated Oscillometric Approach. (2015)
  • Author(s): Keiichiro Yoshinaga, Yuuki Tomiyama, Satoshi Fujii, Saori Nishio, Noriki Ochi, Chietsugu Katoh, Mamiko Inoue, Mutumi Nishida, Keisuke Takeuchi, Yoichi M Ito, Nagara Tamaki.
  • Organizer: AHA 2015
  • Place of Presentation: Orlando
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] 心血管危険因子を有する患者における血液中セロトニン濃度と酸化ストレスの関連 (2015)
  • Author(s): 杉浦知範、土肥靖明、山下純世、藤井 聡、廣渡祐史、大手信之
  • Organizer: 第63回日本心臓病学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2015-09-20
• [Presentation] マクロゴール軟膏によるマトリックスメタロプロテアーゼ-9活性の阻害様式に関する検討 (2015)
  • Author(s): 野田康弘、藤井 聡
  • Organizer: 第17回日本褥瘡学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2015-08-29
• [Presentation] Hypoxia Induces Dysregulation of miR-126 and Affects VEGF and MMP-9 Expression in Endothelial Cells. (2015)
  • Author(s): Satoshi Fujii, Misa Ogasawara, Soichiro Iwaki.
  • Organizer: 2015 Congress of International Society on Thrombosis and Haemostasis.
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2015-06-22
  • Int'l Joint Research
• [Presentation] 褥瘡治療に用いられるブレンド軟膏の吸水性と展延性に関する研究 (2015)
  • Author(s): 藤井聡、、齊藤美加、真川明将、野田康弘、磯貝善蔵、古田勝経
  • Organizer: 第14回日本褥瘡学会北海道地方会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2015-03-14
• [Presentation] GLUCAGON-LIKE PEPTIDE-1 DOWNREGULATES THE EXPRESSION OF TNF-α IN NATURAL KILLER T CELL HYBRIDOMAS (2014)
  • Author(s): Fujii S, Hasegawa R, Ito S
  • Organizer: 第61回日本臨床検査医学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2014-11-23 – 2014-11-25
• [Presentation] Circulating microRNA in patients with coronary artery disease correlates with LDL cholesterol. (2014)
  • Author(s): Fujii S, Sanagawa A.
  • Organizer: 第61回日本臨床検査医学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2014-11-22 – 2014-11-25
• [Presentation] Novel Simple and Accurate Quantitative Endothelial Function Measurements Using Brachial Artery Vascular Volume Elastic Modulus With Automated Oscillometric Approach. (2014)
  • Author(s): Keiichiro Yoshinaga, Yuuki Tomiyama, Saori Nishio, Naoko Matsuoka, Noriki Ochi, Chietsugu Katoh, Mamiko Inoue, Mutumi Nishida, Yoichi M. Ito, Hideo Nishibayashi, Satoshi Fujii, Nagara Tamaki.
  • Organizer: 87th American Heart Association Scientific Session,
  • Place of Presentation: Chicago
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Blood Pressure Reduction and Increase of Circulating MicroRNA-126 Indicate Improvement of Vascular Endothelial Damage after Smoking Cessation Intervention in Middle-aged Habitual Smokers. (2014)
  • Author(s): Sugiura T, Dohi Y, Yamashita S, Iwaki S, Sanagawa A, Ogasawara M, Fujii S, Ohte N.
  • Organizer: 87th American Heart Association Scientific Session,
  • Place of Presentation: Chicago
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] マクロゴールのアルカリフォスターゼ及びマトリックスメタロプロテアーゼ活性に与える影響の酵素学的解析 (2014)
  • Author(s): 真川明将、野田康弘、小林孝志、磯貝善蔵、藤井 聡
  • Organizer: 第16回日本褥瘡学会学術集会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2014-08-29 – 2014-08-30
• [Presentation] 低酸素環境においてスフィンゴ脂質が線溶系に与える分子機構の解析 (2013)
  • Author(s): 藤井 聡、真川 明将、岩城 壮一郎、浅井 萌子、榊原 大輔、山村 周平
  • Organizer: 第35回日本血栓止血学会学術集会
  • Place of Presentation: 山形
• [Presentation] The Expression of Plasminogen Activator Inhibitor Type-1 Is Post-transcriptionally Regulated By Sphingosine-1-phosphate And SERPINE1 mRNA binding protein. (2013)
  • Author(s): Yamamura S, Iwaki S, Sanagawa A, Fujii S.
  • Organizer: The XXIVth Congress of the International Society on Thrombosis and Haemostasis.
  • Place of Presentation: Amsterdam
• [Presentation] ブレンド軟膏（ユーパスタとオルセノン軟膏）の吸水性、ヨウ素の放出性および展延性 (2013)
  • Author(s): 野田 康弘、藤井 聡
  • Organizer: 第15回日本褥瘡学会
  • Place of Presentation: 神戸
• [Presentation] Smoking-Induced Vascular Damage is Associated With Decreased Circulating MicroRNA-126 and Pesistent Elevation of Plasma Serotonin. (2013)
  • Author(s): Sugiura T, Dohi Y, Yamashita S, Ohte N, Hirowatari Y, Ito S, Iwaki S, Fujii S.
  • Organizer: Scientific Session of the American Heart Association.
  • Place of Presentation: Dallas
• [Presentation] HIF-1α/HuR Pathway Regulates the Increased Expression of PAI-1 Induced by Sphingosine 1-phosphate in HepG2 Cells Rendered Hypoxic: A Novel Linkage between Thrombosis and Hypoxia. (2013)
  • Author(s): Sanagawa A, Iwaki S, Asai M, Sakakibara D, Norimoto H, Fujii S.
  • Organizer: Scientific Session of the American Heart Association.
  • Place of Presentation: Dallas