OGAWA Toshihumi

写真a

Affiliation

School of Medicine, Department of Physiology

Job title

Assistant Professor
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Education 【 display / non-display 】

  • 2018
    -
    2023

    Sapporo Medical University   Graduate School of Medicine   地域医療人間総合医学専攻 発生分化・加齢制御医学領域 心血管細胞代謝病態学  

  • 2008
    -
    2014

    Sapporo Medical University   医学部   医学科  

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Research Experience 【 display / non-display 】

  • 2023.04
    -
    Now

    Sapporo Medical University   School of Medicine Medical Sciences   助教

  • 2020.04
    -
    2023.03

    JR札幌病院   循環器内科／腎臓内科／糖尿病内科   医長

  • 2019.04
    -
    2020.03

    札幌循環器病院   内科・循環器内科  

  • 2018.12
    -
    2019.03

    Sapporo Medical University   循環器・腎臓・代謝内分泌内科学講座  

  • 2018.08
    -
    2018.11

    北海道立江差病院   循環器内科  

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Professional Memberships 【 display / non-display 】

  • 2024.02
    -
    Now

    日本肥満学会

  • 2024.01
    -
    Now

    日本生理学会

  • 2022.04
    -
    Now

    日本内分泌学会

  • 2021.05
    -
    Now

    日本心不全学会

  • 2019.12
    -
    Now

    日本糖尿病学会

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Research Areas 【 display / non-display 】

  • Life sciences   Cardiology  

  • Life sciences   Physiology  

  • Life sciences   Metabolism and endocrinology  

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Affiliation 【 display / non-display 】

  • Sapporo Medical University   医学部細胞生理学講座   助教  

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Research Interests 【 display / non-display 】

  • サルコペニア

  • 糖尿病性心筋症

  • 代謝

  • 糖尿病

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Papers 【 display / non-display 】

  • mTOR Inhibitors Modulate the Biological Nature of TGF-β2-Treated or -Untreated Human Trabecular Meshwork Cells in Different Manners.

    Megumi Watanabe, Tatsuya Sato, Toshiyuki Yano, Megumi Higashide, Toshifumi Ogawa, Nami Nishikiori, Masato Furuhashi, Hiroshi Ohguro

    Biomedicines   12 ( 11 )  2024.11  [International journal]

    　View Summary

    Background/Objectives: Mammalian target of rapamycin (mTOR) inhibition may have been suggested to have a beneficial effect on the glaucomatous human trabecular meshwork (HTM). To study the effects of the mTOR inhibitors rapamycin (Rapa) and Torin1 on the glaucomatous HTM, transforming growth factor-β2 (TGF-β2)-treated two-dimensionally (2D) and three-dimensionally (3D) cultured HTM cells were used. Methods: We evaluated (1) the levels of autophagy via Western blot analysis using a specific antibody against microtubule-associated protein 1 light chain 3 (LC3), (2) barrier capacity based on transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) permeability (2D), (3) cellular metabolic functions (2D), (4) the size and stiffness of spheroids, and (5) the mRNA expression of ECM proteins. Results: TGF-β2-induced inhibition of autophagy was significantly inhibited by Rapa and Torin1. Rapa and Torin1 substantially decreased barrier capacity in both TGF-β2-untreated and TGF-β2-treated HTM cells. Cellular metabolic analysis indicated that Rapa, but not Torin1, substantially enhanced both mitochondrial and glycolytic functions of TGF-β2-untreated HTM cells. In the physical properties of spheroids, TGF-β2 resulted in the formation of down-sized and stiffened spheroids. mTOR inhibitors decreased the size but not the stiffness of TGF-β2-untreated spheroids and significantly reduced the TGF-β2-related increase in the stiffness but not the size of spheroids. The diverse effects of mTOR inhibitors on TGF-β2-untreated and TGF-β2-treated spheroids were also observed in the mRNA expression of extracellular matrix proteins. Conclusions: The results taken together suggest that mTOR inhibitors significantly influence the biological aspects of both a single layer and multiple layers of the TGF-β2-treated HTM and untreated HTM.

    DOI PubMed

  • Contribution of MLKL to the development of doxorubicin-induced cardiomyopathy and its amelioration by rapamycin.

    Masaki Shimizu, Wataru Ohwada, Toshiyuki Yano, Hidemichi Kouzu, Tatsuya Sato, Toshifumi Ogawa, Arata Osanami, Yuki Toda, Hiroshi Nagahama, Masaya Tanno, Tetsuji Miura, Atsushi Kuno, Masato Furuhashi

    Journal of pharmacological sciences   156 ( 1 ) 9 - 18  2024.09  [Domestic journal]

    　View Summary

    Necroptosis, necrosis characterized by RIPK3-MLKL activation, has been proposed as a mechanism of doxorubicin (DOX)-induced cardiomyopathy. We showed that rapamycin, an mTORC1 inhibitor, attenuates cardiomyocyte necroptosis. Here we examined role of MLKL in DOX-induced myocardial damage and protective effects of rapamycin. Cardiomyopathy was induced in mice by intraperitoneal injections of DOX (10 mg/kg, every other day) and followed for 7 days. DOX-treated mice showed a significant decline in LVEF assessed by cardiac MRI (45.5 ± 5.1% vs. 65.4 ± 4.2%), reduction in overall survival rates, and increases in myocardial RIPK3 and MLKL expression compared with those in vehicle-treated mice, and those changes were prevented by administration of rapamycin (0.25 mg/kg) before DOX injection. In immunohistochemical analyses, p-MLKL signals were detected in the cardiomyocytes of DOX-treated mice, and the signals were reduced by rapamycin. Mlkl+/- and Mlkl-/- mice were similarly resistant to DOX-induced cardiac dysfunction, indicating that a modest reduction in MLKL level is sufficient to prevent the development of DOX-induced cardiomyopathy. However, evidence of cardiomyocyte necrosis assessed by C9 immunostaining, presence of replacement fibrosis, and electron microscopic analyses was negligible in the myocardium of DOX-treated mice. Thus, MLKL-mediated signaling contributes to DOX-induced cardiac dysfunction primarily by a necrosis-independent mechanism, which is inhibitable by rapamycin.

    DOI PubMed

  • Metabolic dysfunction-associated steatotic liver disease (SLD) and alcohol-associated liver disease, but not SLD without metabolic dysfunction, are independently associated with new onset of chronic kidney disease during a 10-year follow-up period.

    Kazuma Mori, Marenao Tanaka, Tatsuya Sato, Yukinori Akiyama, Keisuke Endo, Toshifumi Ogawa, Toru Suzuki, Hiroki Aida, Wataru Kawaharata, Kei Nakata, Itaru Hosaka, Araya Umetsu, Nagisa Hanawa, Masato Furuhashi

    Hepatology research : the official journal of the Japan Society of Hepatology    2024.08  [International journal]

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    AIMS: The new nomenclature of steatotic liver disease (SLD) including metabolic dysfunction-associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) has recently been proposed. We aimed to elucidate the relationship between each category of SLD and chronic kidney disease (CKD). METHODS: We investigated the effects of various SLDs on the development of CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or positive for urinary protein, during a 10-year period in 12 138 Japanese subjects (men / women, 7984/4154; mean age, 48 years) who received annual health examinations including abdominal ultrasonography. RESULTS: The prevalences of SLD without metabolic dysfunction (SLD-MD[-]), MASLD, MetALD, and ALD were 1.7%, 26.3%, 4.9%, and 1.9%, respectively. During the follow-up period, 1963 subjects (16.2%) (men / women, 1374 [17.2%]/589 [14.2%]) had new onset of CKD. Multivariable Cox proportional hazard model analyses after adjustment of age, sex, eGFR, current smoking habit, diabetes mellitus, hypertension, and dyslipidemia showed that the hazard ratios (HR [95% confidence interval]) for the development of CKD in subjects with MASLD (1.20 [1.08-1.33], p = 0.001) and those with ALD (1.41 [1.05-1.88], p = 0.022), but not those with MetALD (1.11 [0.90-1.36], p = 0.332), were significantly higher than the HR in subjects with non-SLD. Interestingly, subjects with SLD-MD[-] had a significantly lower HR (0.61 [0.39-0.96], p = 0.034) than that in subjects with non-SLD. The addition of the novel classification of SLDs into traditional risk factors for the development of CKD significantly improved the discriminatory capacity. CONCLUSIONS: MASLD and ALD, but not SLD-MD[-], are independently associated with the development of CKD.

    DOI PubMed

  • Fatty Acid-Binding Protein 4-Mediated Regulation Is Pivotally Involved in Retinal Pathophysiology: A Review.

    Hiroshi Ohguro, Megumi Watanabe, Fumihito Hikage, Tatsuya Sato, Nami Nishikiori, Araya Umetsu, Megumi Higashide, Toshifumi Ogawa, Masato Furuhashi

    International journal of molecular sciences   25 ( 14 )  2024.07  [International journal]

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    Fatty acid-binding proteins (FABPs), a family of lipid chaperone molecules that are involved in intracellular lipid transportation to specific cellular compartments, stimulate lipid-associated responses such as biological signaling, membrane synthesis, transcriptional regulation, and lipid synthesis. Previous studies have shown that FABP4, a member of this family of proteins that are expressed in adipocytes and macrophages, plays pivotal roles in the pathogenesis of various cardiovascular and metabolic diseases, including diabetes mellitus (DM) and hypertension (HT). Since significant increases in the serum levels of FABP4 were detected in those patients, FABP4 has been identified as a crucial biomarker for these systemic diseases. In addition, in the field of ophthalmology, our group found that intraocular levels of FABP4 (ioFABP4) and free fatty acids (ioFFA) were substantially elevated in patients with retinal vascular diseases (RVDs) including proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO), for which DM and HT are also recognized as significant risk factors. Recent studies have also revealed that ioFABP4 plays important roles in both retinal physiology and pathogenesis, and the results of these studies have suggested potential molecular targets for retinal diseases that might lead to future new therapeutic strategies.

    DOI PubMed

  • Tirzepatide ameliorates eating behaviors regardless of prior exposure to glucagon-like peptide receptor agonists in Japanese patients with type 2 diabetes mellitus.

    Toru Suzuki, Tatsuya Sato, Marenao Tanaka, Keisuke Endo, Kei Nakata, Toshifumi Ogawa, Itaru Hosaka, Yukinori Akiyama, Araya Umetsu, Masato Furuhashi

    Journal of diabetes and its complications   38 ( 7 ) 108779 - 108779  2024.07  [International journal]

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    AIMS: To investigate effects of tirzepatide, a dual receptor agonist for glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1), on eating behaviors. METHODS: Eating behaviors were evaluated by using a validated questionnaire survey in 33 Japanese patients with type 2 diabetes mellitus (T2DM) (mean age: 51.8 years) who were treated with tirzepatide (2.5 mg/week for 4 weeks and then 5.0 mg/week) for 6 months (M). RESULTS: Treatment with tirzepatide significantly decreased median hemoglobin A1c (HbA1c) (baseline/3 M/6 M: 7.3 %/6.0 %/5.8 %), mean body weight (BW) (baseline/3 M/6 M: 87.7 kg/82.0 kg/79.6 kg) and mean relative score of eating behaviors (baseline/3 M/6 M: 57.0/50.7/45.9). In the GLP-1 receptor agonist (GLP-1RA) naïve group (n = 20, men/women: 13/7), HbA1c and BW were continuously decreased up to 6 M. Changes in eating behaviors were mainly observed in the first 3 M. In the GLP-1RA non-naïve group (n = 13, men/women: 8/5), reductions in HbA1c and BW were predominant in the first 3 M, and changes in eating behaviors were observed up to 6 M. There were no significant correlations of changes in scores of eating behaviors with changes in glycemic control or those in BW. CONCLUSIONS: Tirzepatide ameliorates eating behaviors as well as glycemic management and obesity in Japanese patients with T2DM, and the patterns of improvement are partially dependent on prior exposure to GLP-1RAs.

    DOI PubMed

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Misc 【 display / non-display 】

  • Impact of Mitochondrial Dynamics on Necroptosis in Cardiomyocytes(タイトル和訳中)

    戸田 悠貴, 矢野 俊之, 久野 篤史, 丹野 雅也, 神津 英至, 佐藤 達也, 大和田 渉, 舘越 勇輝, 小川 俊史, 清水 将輝, 古橋 眞人

    日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  88回   PJ080 - 3  2024.03

  • Contribution of MLKL to the Development of Doxorubicin-induced Cardiomyopathy(タイトル和訳中)

    清水 将輝, 大和田 渉, 矢野 俊之, 神津 英至, 佐藤 達也, 長南 新太, 小川 俊史, 戸田 悠貴, 久野 篤史, 丹野 雅也, 古橋 眞人

    日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  88回   PJ073 - 1  2024.03

  • 肥満減量術後慢性期の血糖コントロール悪化にセマグルチドが著効した2型糖尿病の症例

    赤澤 史子, 小川 俊史, 中田 圭, 佐藤 達也, 伊東 竜哉, 竹政 伊知朗, 古橋 眞人

    糖尿病 ( (一社)日本糖尿病学会 )  67 ( 1 ) 37 - 37  2024.01

  • 中枢性尿崩症合併糖尿病患者に対するSGLT2阻害薬+経口GLP1製剤による治療の1例

    中田 圭, 佐藤 達也, 小川 俊史, 大和田 渉, 隅田 健太郎, 神津 英至, 矢野 俊之, 古橋 眞人

    糖尿病 ( (一社)日本糖尿病学会 )  67 ( 1 ) 40 - 40  2024.01

  • チルゼパチドが著効した後腹膜滑膜肉腫合併の若年肥満2型糖尿病の症例

    大久保 武志, 佐藤 達也, 小川 俊史, 中田 圭, 大和田 渉, 隅田 健太郎, 神津 英至, 矢野 俊之, 古橋 眞人

    糖尿病 ( (一社)日本糖尿病学会 )  67 ( 1 ) 38 - 38  2024.01

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Research Projects 【 display / non-display 】

  • AMPデアミナーゼを介する代謝の再配線に着目したサルコペニアの病態の解明

    若手研究

    Project Year :

    2024.04
    -
    2027.03
     

    小川 俊史

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