Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2022.09

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  Now

  Sapporo Medical University   Department of Cardiovascular, Renal and Metabolic Medicine   Professor

Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

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  THE JAPANESE SOCIETY OF INTERNAL MEDICINE

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  日本心臓病学会

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  日本心血管内分泌代謝学会

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  国際高血圧学会

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  日本高血圧学会

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Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Cardiology  

• Life sciences   Metabolism and endocrinology  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   Department of Cardiovascular, Renal and Metabolic Medicine   Professor  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• 慢性炎症

• 耐糖能異常

• Adipokine

• 動脈硬化

• 糖尿病

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Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Prognostic implication of sarcopenia diagnosed by updated Asian Working Group for Sarcopenia criteria in older patients with heart failure: Utility and limitation

  Satoshi Katano, Kotaro Yamano, Toshiyuki Yano, Ryo Numazawa, Ryohei Nagaoka, Suguru Honma, Yusuke Fujisawa, Yasuhiro Miki, Yuhei Takamura, Hayato Kunihara, Hiroya Fujisaki, Hidemichi Kouzu, Katsuhiko Ohori, Masaki Katayose, Akiyoshi Hashimoto, Masato Furuhashi

  The Journal of nutrition, health and aging ( Elsevier BV )  29 ( 1 ) 100434 - 100434  2025.01

  DOI

• A silent interplay between elevated intraocular pressure, glaucoma, and hypertension.

  Tatsuya Sato, Araya Umetsu, Marenao Tanaka, Hiroshi Ohguro, Masato Furuhashi

  Hypertension research : official journal of the Japanese Society of Hypertension    2024.12  [International journal]

  DOI PubMed

• LINC02154 promotes cell cycle and mitochondrial function in oral squamous cell carcinoma.

  Takeshi Niinuma, Hiroshi Kitajima, Tatsuya Sato, Toshifumi Ogawa, Kazuya Ishiguro, Masahiro Kai, Eiichiro Yamamoto, Yui Hatanaka, Iyori Nojima, Mutsumi Toyota, Akira Yorozu, Shohei Sekiguchi, Noritsugu Tohse, Masato Furuhashi, Hiroshi Ohguro, Akihiro Miyazaki, Hiromu Suzuki

  Cancer science    2024.11  [International journal]

  　View Summary

  Long noncoding RNAs (lncRNAs) play pivotal roles in the development of human malignancies, though their involvement in oral squamous cell carcinoma (OSCC) remains incompletely understood. Using The Cancer Genome Atlas (TCGA) dataset, we analyzed expression of 7840 lncRNAs in primary head and neck squamous cell carcinoma (HNSCC) and found that upregulation of LINC02154 is associated with a poorer prognosis. LINC02154 knockdown in OSCC cell lines induced cell cycle arrest and apoptosis, and significantly attenuated tumor growth in vitro and in vivo. Notably, depletion of LINC02154 downregulated FOXM1, a master regulator of cell cycle-related genes. RNA pulldown and mass spectrometry analyses identified a series of proteins that could potentially interact with LINC02154, including HNRNPK and LRPPRC. HNRNPK stabilizes FOXM1 expression by interacting with the 3'-UTR of FOXM1 mRNA, which suggests LINC02154 and HNRNPK promote cell cycling by regulating FOXM1 expression. Additionally, LINC02154 positively regulates HNRNPK expression by inhibiting microRNAs targeting HNRPNK. Moreover, LINC02154 affects mitochondrial function by interacting with LRPPRC. Depletion of LINC02154 suppressed expression of mitochondrial genes, including MTCO1 and MTCO2, and inhibited mitochondrial respiratory function in OSCC cells. These results suggest that LINC02154 exerts its oncogenic effects by modulating the cell cycle and oxidative phosphorylation in OSCC, highlighting LINC02154 as a potential therapeutic target.

  DOI PubMed

• 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

• TGF-β effects on adipogenesis of 3T3-L1 cells differ in 2D and 3D cell culture conditions.

  Araya Umetsu, Megumi Watanabe, Tatsuya Sato, Megumi Higashide, Nami Nishikiori, Masato Furuhashi, Hiroshi Ohguro

  FEBS open bio    2024.10  [International journal]

  　View Summary

  The TGF-β superfamily plays a pivotal role in the regulation of adipogenesis, but little is known about the potential differential role of the three isoforms of TGF-β, TGF-β-1~3. To further elucidate their role, two-dimensionally (2D) and three-dimensionally (3D) cultured 3T3-L1 mouse preadipocytes were subjected to the following analyses: (a) qPCR analysis of adipogenesis-related factors and major extracellular matrix protein (2D and /or 3D), (b) lipid staining by Oil Red O (2D) or BODIPY (3D), (c) Seahorse cellular metabolic measurement (2D), and (d) size and stiffness measurements of 3D 3T3-L1 spheroids. In the 2D cultured 3T3-L1 cells, mRNA expression levels of adipogenesis-related genes and Oil Red O lipid staining intensity were significantly increased by adipogenesis and they were substantially decreased following treatment with 0.1 nm TGF-β isoforms, with TGF-β2 having the greater effects. Consistent with these results, treatment with TGF-β2 resulted in suppression of mitochondrial and glycolytic functions in 2D cultured 3T3-L1 cells. However, the inhibitory effect of TGF-β on adipogenesis decreased under 3D spheroid culture conditions and TGF-β isoforms did not affect adipogenesis-induced (a) enlargement and downsizing of 3T3-L1 spheroids, (b) increase in BODIPY lipid staining intensity, and (c) up-regulation of the mRNA expression of adipogenesis-related genes. The findings presented herein suggest that the three TGF-β isoforms have different suppressive effects on adipogenesis-related cellular properties of 2D cultured 3T3-L1 cells and that their effects decrease under 3D spheroid culture conditions.

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• Small dense LDLコレステロールの推定式の検証と臨床的意義の検討

  遠藤圭佑, 田中希尚, 田中希尚, 佐藤達也, 佐藤達也, 秋山幸功, 小林亮, 田中真輝人, 保坂到, 古橋眞人, 中田圭, 中田圭, 小山雅之, 小山雅之, 大西浩文, 大西浩文, 高橋聡

  日本動脈硬化学会総会・学術集会プログラム・抄録集(Web)   56th  2024

  J-GLOBAL

• 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(Web)   67 ( 1 )  2024

  J-GLOBAL

• Saphenous vein harvesting: Meta-analysis, metaflammation, and adipose tissue remodeling

  Masato Furuhashi, Takuma Mikami, Nobuyoshi Kawaharada, Michael R. Dashwood

  Journal of Cardiac Surgery ( John Wiley and Sons Inc )  36 ( 12 ) 4832 - 4833  2021.12

  Rapid communication, short report, research note, etc. (scientific journal)  

  DOI PubMed

• CKD発症予測におけるfatty liver indexの意義

  高橋 聖子, 田中 希尚, 古橋 眞人, 長南 新太, 宮森 大輔, 後町 結, 塙 なぎさ, 茂庭 仁人, 大西 浩文, 三浦 哲嗣

  日本腎臓学会誌 ( (一社)日本腎臓学会 )  63 ( 4 ) 453 - 453  2021.06

• CKDモデルの造影剤腎症におけるネクロプトーシスの役割

  柴田 智, 茂庭 仁人, 木村 歩, 後町 結, 田中 希尚, 古橋 眞人, 三浦 哲嗣

  日本腎臓学会誌 ( (一社)日本腎臓学会 )  63 ( 4 ) 447 - 447  2021.06

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Awards 【 display / non-display 】

Awards 【 display / non-display 】

• 五島雄一郎賞

  2018   第50回日本動脈硬化学会  

  Winner： 古橋 眞人

• 学術奨励賞

  2014   第35回日本肥満学会  

  Winner： 古橋眞人

• 学術賞

  2013   第36回日本高血圧学会  

  Winner： 古橋眞人

• 高峰譲吉研究奨励賞

  2012   第16回日本心血管内分泌代謝学会  

  Winner： 古橋眞人

• Scholarship Award.

  2008   Keystone Symposia. Molecular Control of Adipogenesis and Obesity.  

  Winner： 古橋眞人

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 脂質シャペロンと代謝性脂肪肝疾患が関わる腎臓病発症機序の解明

  基盤研究(C)

  Project Year :

  2022.04

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  2025.03

   

  田中 希尚, 古橋 眞人

• The association of PCSK7 with coronary calcification

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2020.04

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  2024.03

   

  片岡 有, 古橋 眞人, 小倉 正恒

  　View Summary

  心筋梗塞の原因となる冠動脈石灰化の特徴を解析し、論文報告した。 Atherosclerosis. 2021 Feb;318:70-75. 675例の心筋梗塞症例を解析した。 心筋梗塞を引き起こす冠動脈石灰化は、心臓死や再狭窄、心筋梗塞再発リスクが高いことを報告した。 JACC Case Rep. 2020 Sep 2;2(12):1872-1878.

• Elucidation of intracellular actions of fatty acid-binding protein family and application to clinical therapies

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2020.04

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  2023.03

   

  古橋 眞人

  　View Summary

  1.ヒト脂肪組織由来幹細胞にリコンビナントFABP4を外因性に投与し、RNA-seqを行った。蛋白~蛋白相互作用カスケード解析から様々な転写因子および 各種キナーゼとの相互作用が認められた。 2.ヒト脂肪組織由来幹細胞にリコンビナントFABP4を外因性に投与し、CE-TOFMSおよびLC-TOFMSを用いてメタボローム解析を行った。FABP4の外因性投与により、 様々な細胞内メタボライトの変化が認められ、FABP4が脂肪細胞由来の生理活性物質であるアディポカインとして働くことが確認された。 3.リコンビナントFABP4に対する各種脂肪酸(パルミチン酸、パルミトレイン酸、ステアリン酸、オレイン酸、リノール酸、αリノレイン酸、アラキドン酸、エ イコサペンタエン酸、ドコサヘキサエン酸)に対する脂肪酸結合親和性を1-anilinonapthalene 8-sulfonic acid (1,8 ANS)を用いて行ったところ、通常状態で は脂肪酸結合親和性は必須脂肪酸で、多価不飽和脂肪酸であるリノール酸やαリノレイン酸に親和性が高く、飽和脂肪酸であるパルミチン酸とは親和性が低かった。また、酸化ストレスを模倣するフリーラジカルジェネレーターである2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)の存在下ではパルミチン酸 以外の脂肪酸はKd値が上昇し、親和性が相対的に低くなったが、パルミチン酸とのKd値は変化がなかった。 4. リコンビナントFABP4を各種細胞に投与して、炎症関連分子の変化を確認した。 5.疫学調査 (端野・壮瞥町研究) でFABP4濃度を測定し、12年間のフォロー期間中の心血管死と関連することを見出した。 6.ヒトの心臓手術時に採取した心外膜脂肪組織や血管周囲脂肪組織の検討からFABP4の発現を確認した。

• Elucidation of underlying mechanism of the onset and renal deterioration of kidney disease contributed by lipid chaperones

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2019.04

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  2022.03

   

  Marenao Tanaka

  　View Summary

  In a renal biopsy cohort, urinary FABP4 excretion was associated with renal function, urinary protein levels and deterioration of renal function after 1 year. In a general population cohort, a high LDL-cholesterol level was negatively associated with change in eGFR during 10-year follow-up period and was a risk factor for the development of CKD in males. In IgA nephropathy and gddY, a IgAN-prone mouse model, expression of FABP4 was ectopically induced by glomerular injury in cells of the glomerulus including glomerular endothelial cells and macrophages, and the extent of glomerular FABP4 expression was associated with proteinuria and renal dysfunction. Expression of ER stress markers were present on the cells in glomerulus in IgAN and in gddY. In human renal glomerular endothelial cells, FABP4 was induced by treatment with VEGF and was secreted from cells. Treatment of podocytes with FABP4 significantly increased gene expression of inflammatory cytokines and ER stress markers.

• Elucidation of ectopic expression of fatty acid-binding protein 4 in endovascular injury and application to clinical therapies

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2017.04

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  2020.03

   

  Furuhashi Masato

  　View Summary

  Fatty acid-binding protein 4 (FABP4) is expressed in adipocytes and macrophages and plays significant roles in the development of insulin resistance and atherosclerosis. The present study demonstrated that FABP4 was ectopically induced in endothelial cells by cellular senescence and vascular injury. Furthermore, secreted FABP4 from injured vascular endothelial cells promoted inflammatory response in several cells, proliferation and migration in vascular smooth muscle cells, and endothelial dysfunction in vascular endothelial cells, leading to the development of neointima formation after vascular injury.

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