OSANAI Makoto

写真a

Affiliation

School of Medicine, Department of Pathology (2)

Job title

Professor
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Education 【 display / non-display 】

  • 　
    -
    1997

    Asahikawa Medical University   医学研究科  

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    1997

    Asahikawa Medical College  

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    1993

    Asahikawa Medical University   School of Medicine   Medical Course  

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Degree 【 display / non-display 】

  • MD, PhD

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Professional Memberships 【 display / non-display 】

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    Japanese Society of Pathology

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    日本癌学会

  • 　
    　
    　

    日本病理学会

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    Japanese Cancer Association

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Research Areas 【 display / non-display 】

  • Life sciences   Cell biology  

  • Life sciences   Experimental pathology  

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Affiliation 【 display / non-display 】

  • Sapporo Medical University School of Medicine   DEpartment of Pathology   Professor  

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Research Interests 【 display / non-display 】

  • 細胞接着

  • アポトーシス

  • タイト結合

  • 細胞極性

  • ビタミンＤ

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Papers 【 display / non-display 】

  • Common pathological findings in the heart in COVID-19-related sudden death cases: An autopsy case series.

    Daisuke Kyuno, Masatoshi Tateno, Yusuke Ono, Kazufumi Magara, Kumi Takasawa, Akira Takasawa, Makoto Osanai

    Heliyon   9 ( 10 ) e20564  2023.10  [International journal]

    　View Summary

    BACKGROUND: Cardiomyopathy is a leading cause of sudden out-of-hospital death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination. Such unexpected COVID-19-related cardiomyopathies are challenging to diagnose as specific pathological findings are not always identified. CASE SUMMARY: We reported the autopsy findings of two cases of sudden death due to COVID-19-related cardiomyopathies. In one case, death occurred after SARS-CoV-2 infection, while in the other, after COVID-19 vaccination. We found common pathological findings in both hearts: decreased staining intensity with special stains, loss of rhabdomeres, and multivacuolation in cardiomyocytes without inflammatory cell infiltration. The remaining organs showed no findings that could have contributed to the deaths. CONCLUSION: In cases of sudden death after SARS-CoV-2 infection or COVID-19 vaccination, the decreased staining intensity with special stains may aid the diagnosis of sudden death due to COVID-19-related cardiomyopathy, even when H&E staining shows few findings.

    DOI PubMed

  • 癌幹細胞マーカーに対する自己抗体を利用した乳癌患者の予後予測(Prediction of Prognosis in Breast Cancer Patients Using Autoantibodies to Cancer Stem Cell Markers)

    及能 大輔, 廣橋 良彦, 和田 朝香, 島 宏彰, 九冨 五郎, 真柄 和史, 高澤 久美, 高澤 啓, 竹政 伊知朗, 小山内 誠

    日本癌学会総会記事 ( (一社)日本癌学会 )  82回   2116 - 2116  2023.09

  • Emerging roles of transmembrane-type tight junction proteins in cancers.

    Akira Takasawa, Kumi Takasawa, Masaki Murata, Makoto Osanai, Norimasa Sawada

    Pathology international   73 ( 8 ) 331 - 340  2023.08  [International journal]

    　View Summary

    Tight junctions (TJs) are the most apical components of the cell-cell adhesion machinery in epithelial and endothelial cells and they play essential roles in homeostasis. Recent studies have revealed that aberrant expression of tight junction proteins (TJPs) is frequently observed in various type of cancers. Here we review cancer-associated aberrant expression of TJPs with focus on transmembrane-type TJPs including claudins, junctional adhesion molecule-A (JAM-A), and occludin. Some transmembrane-type TJPs are upregulated at the early neoplastic stage and their expression persists during dedifferentiation. Aberrant expression of TJPs contributes to proliferation, invasion, and dysregulated signaling of cancer cells. In addition to an increase in their expression level, their localization is altered from a TJ-restricted pattern to distribution throughout the whole cell membrane, making them suitable as therapeutic targets. Extracellular domains of transmembrane-type TJPs can be approached by target drugs not only from the lumen side (apical side) but also from the extracellular matrix side (basal side), including blood vessels. Aberrantly expressed TJPs are potential useful diagnostic markers as well as therapeutic targets for cancers.

    DOI PubMed

  • MPNSTにおけるPVR発現の意義

    中橋 尚也, 高澤 啓, 江森 誠人, 高澤 久美, 太田 未咲, 真柄 和史, 小野 佑輔, 及能 大輔, 杉田 真太朗, 長谷川 匡, 小山内 誠

    日本整形外科学会雑誌 ( (公社)日本整形外科学会 )  97 ( 8 ) S1975 - S1975  2023.08

  • Establishment and characterization of a novel dedifferentiated chondrosarcoma cell line, SMU-DDCS, harboring an IDH1 mutation

    Makoto Emori, Naoya Nakahashi, Akira Takasawa, Kenji Murata, Yasutaka Murahashi, Junya Shimizu, Tomohide Tsukahara, Shintaro Sugita, Kohichi Takada, Tadashi Hasegawa, Makoto Osanai, Kosuke Iba

    Human Cell ( Springer Science and Business Media LLC )   2023.07

    DOI

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Books and Other Publications 【 display / non-display 】

  • The tight junction, intercellular seal as a cell-signaling player; Protocols for examination for its status.

    Elsevier  2010

  • Tight junctions and cancer development, Encyclopedia of Cancer. M. Schwab Osanai M

    Springer  2008

  • Expression of carbohydrate antigens in pancreatic cancer: Handbook of immunohistochemistry and in situ hybridization of human carcinomas. MA. Hayat. Osanai M

    Elsevier  2006

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Misc 【 display / non-display 】

  • 膵癌患者の予後と癌進展におけるJAM-Aの役割(Junctional Adhesion Molecule-A may play a role in the progression of pancreatic cancer)

    及能 大輔, 高澤 啓, 高澤 久美, 真柄 和史, 小山内 誠

    日本癌学会総会記事 ( (一社)日本癌学会 )  81回   J - 2053  2022.09

  • タイト結合分子JAM-Aの異常高発現が乳がんの悪性化に関与する(Elevated expression of JAM-A contributes malignant progression of breast cancer)

    真柄 和史, 高澤 啓, 高澤 久美, 及能 大輔, 小山内 誠

    日本癌学会総会記事 ( (一社)日本癌学会 )  81回   P - 3247  2022.09

  • 両側肺の壊死組織周囲への黒色色素、シュウ酸カルシウム結晶の沈着をともなった深在性真菌症の一剖検例

    久保田 雄策, 小野 佑輔, 高澤 啓, 多田 聡法, 真柄 和史, 青山 智志, 及能 大輔, 高澤 久美, 小山内 誠

    日本病理学会会誌 ( (一社)日本病理学会 )  111 ( 1 ) 357 - 357  2022.03

  • ビタミンD代謝酵素CYP24A1は乳癌に対する新規治療標的である

    紙谷 咲良, 仲盛 優菜, 真柄 和史, 小野 佑輔, 及能 大輔, 高澤 久美, 高澤 啓, 小山内 誠

    日本病理学会会誌 ( (一社)日本病理学会 )  111 ( 1 ) 354 - 354  2022.03

  • 膵臓癌におけるALDOA発現とその意義

    永井 美佐, 小野 佑輔, 高澤 啓, 永井 佐和, 真柄 和史, 青山 智志, 及能 大輔, 高澤 久美, 小山内 誠

    日本病理学会会誌 ( (一社)日本病理学会 )  111 ( 1 ) 352 - 352  2022.03

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Industrial Property Rights 【 display / non-display 】

  • 糖尿病網膜症の予防治療薬. 澤田典均、小山内誠、錦織奈美

    Patent

    　View Summary

    2005-280166

  • 白内障の予防及び/又は治療のための医薬. 澤田典均、小山内誠、錦織奈美

    Patent

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    2006-258252

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Research Projects 【 display / non-display 】

  • レチノイン酸特異的代謝酵素CYP26のレチノイン酸非依存性がん悪性化機構の解明

    基盤研究(C)

    Project Year :

    2022.04
    -
    2025.03
     

    小野 佑輔, 高澤 啓, 小山内 誠

  • Retinoic acid-deficient renal mesangial cells are responsible for the development of diabetic nephropathy

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2017.04
    -
    2020.03
     

    Osanai Makoto

    　View Summary

    Diabetic nephropathy is the greatest single cause of hemodialysis due to renal failure. Here we propose that glomerular endothelial tight junctions (TJs) are plausible therapeutic targets for diabetic nephropathy because TJs primarily determine the vascular permeability. Indeed, mesangial cell-derived cytokines limit vascular leakiness of capillaries and eventually attenuate the breakdown of vascular integrity in diabetic angiopathy. We found that CYP26A1, an enzyme specifically involved in metabolic inactivation of retinoic acid (RA), is highly expressed in diabetic glomeruli. We also found that the state of reduced RA bioavailability caused by enhanced expression of CYP26A1 is sufficient to increase vascular permeability and causally leads to glomerular fibrosis and sclerosis. Our observations provide substantial evidence for deteriorating factor of CYP26A1 in diabetic angiopathy, and suggest mechanisms whereby RA deficient-mesangial cells might promote diabetic nephropathy.

  • Nuclear receptors as molecular regulator and chemopreventive targets of colon cancer stem cells.

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2011
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    2013
     

    MASUDA Sonoko, TANAKA Takuji, OSANAI Makoto, TERASAKI Masaru

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    Increasing evidence suggests that colon cancer stem cells (CCSC) have responsible for carcinogenesis, cancer development and recurrence. To establish signaling pathways in CCSC, which are implicated in the initiation and progression of colon cancer, we examined nuclear receptor signaling in colonospheres that are enriched in CCSC from established cell lines. We found that colonospheres formed by colon cancer cell lines are highly enriched in CCSC and that Wnt/b-catenin pathway plays a critical role in growth and maintenance of colonospheres. We also found that the combination of Fucoxanthinol and 1a,25-dihydroxyvitamin D3 acts on the CCSC cell growth through down-regulation of PPARg and NFkB p52, and as an intrinsic factor for the prevention of colon cancer. These findings establish a critical role for PPARg and vitamin D receptor (VDR) in growth regulation in colon cancer cells via functionally relevant cross-talk between these nuclear signaling pathways.

  • Retinoic acid metabolizing enzyme CYP26A1 is a candidate oncogene, and a possible therapeutic target for cancers.

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2008
    -
    2010
     

    OSANAI Makoto, LEE Gang-Hong

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    Vitamin A deficiency (VAD) is associated with increased susceptibility to carcinogenesis in animal models and elevated risk for a number of human cancers. We found that the CYP26A1, the gene encoding a cytochrome P450 enzyme specifically involved in metabolic inactivation of retinoic acid (RA), the most active vitamin A derivative, is highly expressed in a number of variety types of cancer, including primary breast carcinomas. We also found that the state of reduced RA bioavailability caused by enhanced expression of CYP26A1 is sufficient to markedly increase tumorigenic and metastatic potential. Our observations provide strong evidence for oncogenic and cell survival properties of CYP26A1 in carcinogenesis, and suggest mechanisms whereby VAD might promote cancer development. We believe that specific drug-mediated inactivation of CYP26A1 may have a notable impact on malignant potential of human tumors, and these results show its potential feasibility of CYP26A1-inhibitory cancer therapies.

  • Biological barrier and human diseases

    Grant-in-Aid for Scientific Research (B)

    Project Year :

    2005
    -
    2007
     

    KOJIMA Takashi, CHIBA Hideki, TOBIOKA Hrotoshi, MURATA Masaki

    　View Summary

    In this project, we have been trying to expand understanding of molecular regulation of tight junctions to human diseases, as follows. 1. Orphan nuclear receptor HNF-4alpha is shown to induce various kinds of tight junction proteins including claudins and microvilli component EBP-50, resulted in formation of microvilli as well as tight junctions. 2. Permeability of blood-retinal barrier is well known to increase with advance of diabetic retinopathy. We showed that retinoic acid, in particular RAR-alpha ligand, prevent the increase of the permeability by production of GDNF in astrocytes. 3. The epithelial barrier of the upper respiratory tract, which is the first site of exposure to inhaled antigens, plays a crucial role in host defense in terms of innate immunity. The epithelium of the nasal mucosa forms a continuous barrier against a wide variety of exogenous antigens by tight junctions. We first found that expression of dendritic cell activator TSLP is significantly increased in patients with nasal allergy. Thus to study the mechanisms involved in nasal allergy, we first established a culture method to passage human nasal epithelial cells using hTERT. These cultures express claudin-1, -4, -7, like the cells in vivo. Using these cultures, we demonstrate that TLR-2 ligand induces TSLP production. On the other hand, we found that TSLP induced expression of claudin-7. These results suggest dendritic cells tightly contact with nasal epithelium. 4. Ca^<2+> is considered to be absorbed across intestinal epithelial monolayers via transcellular and paracellular pathways. We show, by using vitamin V receptor knockout mice, RNA interference and overexpression strategies, that claudin-2 and claudin-12 contribute to paracellular Ca^<2+> absorption in intestinal epithelial cells. We also provide evidence showing that expression of claudins 2 and 12 is upregulated in enterocytes in vitro and in vivo by 1α,25 (OH)_2D_3 through its receptor VDR.

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