Updated on 2025/04/15

写真a

 
OSHIMA Kenzi
 
Organization
Graduate School of Bioagricultural Sciences Department of Applied Biosciences Assistant Professor
Graduate School
Graduate School of Bioagricultural Sciences
Undergraduate School
School of Agricultural Sciences
Title
Assistant Professor

Degree 1

  1. Ph. D. ( 2002.3   Nagoya University ) 

Research Interests 1

  1. milk, epithelial cell, MFGM, exosome, extracellular vesicle, gut microbiota

Research Areas 1

  1. Life Science / Nutrition science and health science  / milk, epithelial cells, extracellular vesicles, gut microbiota

Current Research Project and SDGs 1

  1. 腸内環境による代謝・免疫の長期持続調節の研究

Research History 3

  1. Nagoya University,   Assistant Professor

    2011.3

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    Country:Japan

  2. the University of Chicago   Department of Molecular Genetics and Cell Biology   Research Associate

    2007.7 - 2011.2

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    Country:United States

  3. RIKEN CDB   Researcher

    2002.4 - 2007.6

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    Country:Japan

Education 1

  1. Nagoya University   Graduate School, Division of Agriculture

    1999.4 - 2002.3

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    Country: Japan

Professional Memberships 3

  1. 日本分子生物学会

  2. 日本農芸化学会

  3. 日本栄養・食糧学会

 

Papers 37

  1. Vitamin C deficiency alters the transcriptome of the rat brain in a glucocorticoid-dependent manner, leading to microglial activation and re duce d neurogenesis

    Goto, S; Kojima, N; Komori, M; Kawade, N; Oshima, K; Nadano, D; Sasaki, N; Horio, F; Matsuda, T; Miyata, S

    JOURNAL OF NUTRITIONAL BIOCHEMISTRY   Vol. 128   page: 109608   2024.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jnutbio.2024.109608

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    PubMed

  2. FcRY is a key molecule controlling maternal blood IgY transfer to yolks during egg development in avian species

    Okamoto, M; Sasaki, R; Ikeda, K; Doi, K; Tatsumi, F; Oshima, K; Kojima, T; Mizushima, S; Ikegami, K; Yoshimura, T; Furukawa, K; Kobayashi, M; Horio, F; Murai, A

    FRONTIERS IN IMMUNOLOGY   Vol. 15   page: 1305587   2024.2

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.3389/fimmu.2024.1305587

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  3. Characterization of human Ccser2 as a protein tracking the plus-ends of microtubules

    Shirai, Y; Okuda, T; Oshima, K; Nadano, D

    BMC RESEARCH NOTES   Vol. 16 ( 1 ) page: 198   2023.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1186/s13104-023-06475-z

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  4. 乳児マウス消化管の発達に伴うラクトフェリンの消化吸収の変化の解析

    石川千尋, 伊藤南帆, 灘野大太, 松田幹, 大島健司

    ラクトフェリン 2021・2023     page: 33 - 37   2023.8

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    Authorship:Last author   Language:Japanese   Publishing type:Research paper (conference, symposium, etc.)  

  5. Hyaluronan degradation and release of a hyaluronan-aggrecan complex from perineuronal nets in the aged mouse brain

    Sugitani, K; Egorova, D; Mizumoto, S; Nishio, S; Yamada, S; Kitagawa, H; Oshima, K; Nadano, D; Matsuda, T; Miyata, S

    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS   Vol. 1865 ( 2 ) page: 129804   2021.2

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbagen.2020.129804

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  6. A pericellular hyaluronan matrix is required for the morphological maturation of cortical neurons

    Takechi, M; Oshima, K; Nadano, D; Kitagawa, H; Matsuda, T; Miyata, S

    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS   Vol. 1864 ( 10 ) page: 129679   2020.10

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    DOI: 10.1016/j.bbagen.2020.129679

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  7. Transcription Factor Sox4 as a Potential Player in Mammary Gland Involution

    Shibayama Hirohisa, Yamamoto Tomomi, Oshima Kenzi, Matsuda Tsukasa, Nadano Daita

    DNA AND CELL BIOLOGY   Vol. 38 ( 10 ) page: 1125 - 1133   2019.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1089/dna.2019.4700

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  8. 腸上皮 Caco-2 細胞単層培養の頂端側におけるラクトフェリンの取り込みとビフィズス菌増殖促進ペプチドを含む分解断片の放出( Invited

    秋山友香、西尾俊亮、大島健司、織田浩嗣、山内恒治、阿部文明、松田幹

    ラクトフェリン 2019     2019.5

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    Language:Japanese   Publishing type:Research paper (conference, symposium, etc.)  

  9. 乳に含まれる細胞外小胞と酸性リン脂質結合タンパク質の新たな機能

    大島 健司

    化学と生物   Vol. 57 ( 4 ) page: 205 - 206   2019.4

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:公益社団法人 日本農芸化学会  

    DOI: 10.1271/kagakutoseibutsu.57.205

    CiNii Research

  10. Apical-to-basolateral transepithelial transport of cow's milk caseins by intestinal Caco-2 cell monolayers: MS-based quantitation of cellularly degraded alpha- and beta-casein fragments

    Sakurai Nao, Nishio Shunsuke, Akiyama Yuka, Miyata Shinji, Oshima Kenzi, Nadano Daita, Matsuda Tsukasa

    JOURNAL OF BIOCHEMISTRY   Vol. 164 ( 2 ) page: 113 - 125   2018.8

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/jb/mvy034

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  11. The mRNA-binding protein Serbp1 as an auxiliary protein associated with mammalian cytoplasmic ribosomes

    Muto Akiko, Sugihara Yoshihiko, Shibakawa Minami, Oshima Kenzi, Matsuda Tsukasa, Nadano Daita

    CELL BIOCHEMISTRY AND FUNCTION   Vol. 36 ( 6 ) page: 312 - 322   2018.8

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/cbf.3350

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  12. Extracellular vesicle-mediated MFG-E8 localization in the extracellular matrix is required for its integrin-dependent function in mouse mammary epithelial cells

    Ooishi Takuya, Nadano Daita, Matsuda Tsukasa, Oshima Kenzi

    GENES TO CELLS   Vol. 22 ( 10 ) page: 885 - 899   2017.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/gtc.12521

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  13. Analysis of membrane microvesicle binding proteins using density gradient centrifugation and SDS-PAGE

    Nakatani Hajime, Yasueda Takehiko, Oshima Kenzi, Matsuda Tsukasa

    Electrophoresis Letters   Vol. 61 ( 2 ) page: 115 - 119   2017

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Japanese Electrophoresis Society  

    <p>Milk contains two kinds of secretory membrane microvesicles, milk fat globule and exsosome. Using SDS-PAGE in combination with density gradient ultracentrifugation, a phosphatidyl serine (PS)-binding membrane protein, MFG-E8, of these membrane vesicles in mouse milk was investigated. Milk fat globules and exosomes in fresh milk from lactating mice were recovered mainly from the lower density (~1.0) fractions and higher density (1.07~1.13) fractions, respectively, and MFG-E8 distributed to the milk fat globule fractions. Such MFG-E8 distribution was changed after forced weaning (pups withdrawal), i.e., MFG-E8 was present in not only the milk fat globule fractions but also a wide density-range (1.0~1.1) of the fractions including the exosome fractions and soluble protein fractions. Fluorescence microscopy analysis of the milk fat globules using anti-MFG-E8 antibody and annexin V as a PS probe showed that both of MFG-E8 and PS on the surface of milk fat globules largely differed even in fresh milk, and increased both in vivo with time after weaning and in vitro during the milk incubation. Mammary epithelial cells are known as non-professional phagocytes, which play a role in clearance of neighboring apoptotic cells on the epithelial cell turnover in lactating mammary glands. Mammary epithelial HC-11 cells preferentially phagocytosed old milk-fat globules rich in the surface MFG-E8 and, moreover, such phagocytosis was inhibited by anti-MFG-E8 antibody. We hypothesize that mammary epithelial cells may remove aged milk fat globules labeled heavily with MFG-E8 from breast milk and maintain freshness of milk lipids as an important nutrient for nursing infants.</p>

    DOI: 10.2198/electroph.61.115

    CiNii Research

  14. Evaluation of allergenic potential for rice seed protein components utilizing a rice proteome database and an allergen database in combination with IgE-binding of recombinant proteins Reviewed

    Kana Hirano, Shingo Hino, Kenzi Oshima, Daita Nadano, Atsuo Urisu, Fumio Takaiwa & Tsukasa Matsuda.

    Biosci Biotechnol Biochem.   Vol. 80 ( 3 ) page: 564-73   2016.1

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    DOI: 10.1080/09168451.2015.1116927

  15. A protective effect of milk fat globule EGF factor VIII (MFG-E8) on the spontaneous fusion of milk fat globules in breast milk. Reviewed

    Takehiko Yasueda, Kenzi Oshima, Hajime Nakatani, Kanji Tabuchi, Daita Nadano and Tsukasa Matsuda.

    Journal of Biochemistry   Vol. 158 ( 1 ) page: 25 - 35   2015.7

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    DOI: 10.1074/jbc.M114.598821

  16. A Transport and Retention Mechanism for the Sustained Distal Localization of Spn-F-IKKε During Drosophila Bristle Elongation. Reviewed International coauthorship

    Tetsuhisa Otani, Kenzi Oshima, Akiyo Kimpara, Michiko Takeda, Uri Abdu, Shigeo Hayashi

    Development   Vol. 142 ( 13 ) page: 2338 - 2351   2015.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1242/dev.121863

  17. Glycosylated Chicken ZP2 Accumulates in the Egg Coat of Immature Oocytes and Remains Localized to the Germinal Disc Region of Mature Eggs. Reviewed

    Shunsuke Nishio, Yoshinori Kohno, Yuki Iwata, Mayumi Arai, Hiroki Okumura, Kenzi Oshima, Daita Nadano, and Tsukasa Matsuda.

    Biol Reprod.   Vol. 91 ( 5 ) page: 107   2014.11

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  18. Lyar, a cell growth-regulating zinc finger protein, was identified to be associated with cytoplasmic ribosomes in male germ and cancer cells. Reviewed

    Kahori Yonezawa, Yoshihiko Sugihara, Kenzi Oshima, Tsukasa Matsuda, Daita Nadano.

    Mol Cell Biochem.   Vol. 395 ( 1 ) page: 221-229   2014.10

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    DOI: 10.1007/s11010-014-2128-x

  19. Macroglobulin complement-related encodes a protein required for septate junction organization and paracellular barrier function in Drosophila. Reviewed

    Sonia Hall, Courtney Bone, Kenzi Oshima, Liang Zhang, Molly McGraw, Bethany Lucas, Richard G. Fehon and Robert E. Ward IV.

    Development   Vol. 141 ( 4 ) page: 889-898   2014.2

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  20. A lactoferrin-receptor, intelectin 1, affects uptake, sub-cellular localization and release of immunochemically detectable lactoferrin by intestinal epithelial Caco-2 cells. Reviewed

    Akiyama Y, Oshima K, Kuhara T, Shin K, Abe F, Iwatsuki K, Nadano D, Matsuda T.

    The Journal of Biochemistry.   Vol. 154 ( 5 ) page: 437-448.   2013.11

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  21. ラクトフェリン受容体を高発現するヒト腸上皮様Caco-2細胞における牛乳ラクトフェリンの取り込みと断片化および放出

    秋山友香、大島健司、久原徹哉、新 光一郎、灘野大太、 阿部文明、松田 幹

    ラクトフェリン2013     page: 1-6   2013.10

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    Language:Japanese   Publishing type:Research paper (bulletin of university, research institution)  

  22. Allergenic potential of rice-pollen proteins: expression, immuno-cross reactivity and IgE-binding. Reviewed

    Hirano K, Hino S, Oshima K, Okajima T, Nadano D, Urisu A, Takaiwa F, Matsuda T

    The Journal of Biochemistry.   Vol. 154 ( 2 ) page: 195-205   2013.8

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  23. Identification and expression of an autosomal paralogue of ribosomal protein S4, X-linked, in mice: Potential involvement of testis-specific ribosomal proteins in translation and spermatogenesis. Reviewed

    Sugihara Y, Sadohara E, Yonezawa K, Kugo M, Oshima K, Matsuda T, Nadano D.

    Gene   Vol. 521 ( 1 ) page: 91-99   2013.5

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  24. Intracellular Retention and Subsequent Release of Bovine Milk Lactoferrin Taken Up by Human Enterocyte-Like Cell Lines, Caco-2, C2BBe1 and HT-29. Reviewed

    Yuka AKIYAMA, Kenzi OSHIMA, Kouichirou SHIN, Hiroyuki WAKABAYASHI, Fumiaki ABE, Daita NADANO, Tsukasa MATSUDA

    Bioscience, Biotechnology, and Biochemistry   Vol. 77 ( 5 ) page: 1023 - 1029   2013.5

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    DOI: https://doi.org/10.1271/bbb.121011

  25. Dephosphorylation reduces passage of ovalbumin antigen through intestinal epithelial Caco-2 cell monolayers. Reviewed

    Matsubara T, Akiyama Y, Oshima K, Okajima T, Nadano D, Matsuda T.

    The Journal of Biochemistry.   Vol. 153 ( 4 ) page: 347-354   2013.4

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    DOI: 10.1093/jb/mvs154

  26. Post-weaning increases in the milk-fat globule EGF-factor VIII (MFG-E8) on fat globules in mouse milk and in the uptake of the fat globules by HC11 mammary epithelial cells. Reviewed International coauthorship

    Hajime Nakatani, Takehiko Yasueda, Kenzi Oshima, Tetsuya Okajima, Daita Nadano, David J Flint, and Tsukasa Matsuda.

    Journal of biochemistry     2013.1

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    Milk fat globules (MFGs) secreted by lactating mammary gland are unique lipid surrounded by a phospholipid bi-layer. We report here post-weaning changes in milk fat globule EGF factor VIII (MFG-E8) and annexin V-accessible phosphatidylserine on the surface of MFGs. The MFG content in milk markedly decreased to about half within 2 days after forced weaning, despite a slight increase in milk protein content. Immunofluorescence-staining of MFGs using anti-MFG-E8 and annexin V indicated that MFG-E8 was present on some, but not all, MFGs before weaning, whereas most of MFGs were MFG-E8-positive and annexin V-negative after weaning. Free MFG-E8 with binding activity to phosphatidylserine was present abundantly in the post-weaning milk, and indeed exhibited binding to MFGs in pre-weaning milk. MFGs were taken up by HC11 mouse mammary epithelial cells in vitro, and those from post-weaning milk were remarkable for such cellular uptake. Moreover, the uptake of MFGs by the cells was inhibited by an anti-MFG-E8 antibody. Taken together, these findings suggest that MFG-E8 plays a critical role in regulation of MFG dynamics after weaning or during the suckling interval through the control of MFG-epithelial cell interaction in lactating mammary glands.

    DOI: 10.1093/jb/mvs116

  27. Re-Evaluation of Milk-Fat Globule EGF-Factor VIII (MFG-E8) as an Intrinsic Component of the Mouse Milk-Fat Globule Membrane. Reviewed

    Nakatani, Hajime and Yasueda, Takehiko and Oshima, Kenzi and Nadano, Daita and Matsuda, Tsukasa

    Bioscience, biotechnology, and biochemistry     2012.11

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    In lactating mammary glands, milk fat is secreted as fat globules surrounded by a cell plasma membrane containing characteristic membrane-associated proteins. Among these, butyrophilin has been shown to be specific and intrinsic to the fat globule membrane, whereas milk-fat globule EGF-factor VIII (MFG-E8) is uncertain. We characterized in the present study MFG-E8 in milk fat globules and in the culture medium of HC11 mammary epithelial cells. MFG-E8 was immunologically detected in the mammary tissues of both pregnant and lactating mice. Double-immunofluorescence staining for MFG-E8 and butyrophilin showed diversity in the MFG-E8-staining intensity among different fat globules in milk. HC11 cells secreted monomeric MFG-E8 with phosphatidylserine-binding activity, despite no fat globules being detected in the cells. This secretion was upregulated by not only prolactin but also by insulin or EGF. These results suggest that milk MFG-E8 was not equally present among fat globules and not necessarily intrinsic to the fat globules.

    DOI: 10.1271/bbb.120412

  28. Discharge of solubilized and Dectin-1-reactive [beta]-glucan from macrophage cells phagocytizing insoluble [beta]-glucan particles: involvement of reactive oxygen species (ROS)-driven degradation. Reviewed

    Shingo Hino; Aki Kito; Remi Yokoshima; Ryosuke Sugino; Kenzi Oshima; Tatsuya Morita; Tetsuya Okajima; Daita Nadano; Koji Uchida;Tsukasa Matsuda.

    Biochem Biophys Res Commun   Vol. 421 ( 2 ) page: 329–334   2012.5

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    ... These results suggest that degraded but Dectin - 1 - reactive β- glucan is discharged from macrophage cells ... ROS -production inhibitors reduced soluble β- glucan discharge from the ... Soluble β- glucan produced by in vitro ROS - driven degradation activated macrophages . ...

    DOI: 10.1016/j.bbrc.2012.04.009

  29. The murine Gcap14 gene encodes a novel microtubule binding and bundling protein. Reviewed

    Hosono, Hitomi and Yamaguchi, Nao and Oshima, Kenzi and Matsuda, Tsukasa and Nadano, Daita

    FEBS letters   Vol. 586 ( 10 ) page: 1426--1430   2012.5

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    Microtubules form flexible fibers, which are utilized in cell proliferation and differentiation. Although the flexibility of microtubules was shown to be regulated by various microtubule-associated proteins, this regulation is still far from complete understanding. Here, we report a new potential regulator of microtubules in mammals. Gcap14 colocalizes with microtubules in mammalian cells transfected with Gcap14 expression vector. Association of Gcap14 with microtubules was confirmed by biochemical subcellular fractionation. Recombinant Gcap14 protein cosedimented with pure microtubules, indicating a direct binding between the two. Furthermore, recombinant Gcap14 was shown to have the ability of inducing microtubule bundling in vitro.

    DOI: 10.1016/j.febslet.2012.04.008

  30. Analysis of protein dynamics within the septate junction reveals a highly stable core protein complex that does not include the basolateral polarity protein Discs large Reviewed

    K Oshima, R G Fehon

    J. Cell Sci.   Vol. 124 ( 16 ) page: 2861-2871   2011.8

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1242/jcs.087700

  31. IKKε regulates cell elongation through recycling endosome shuttling. Reviewed

    Otani, T, Oshima, K, Onishi, S, Takeda, M, Shinmyozu, K, Yonemura, S, Hayashi, S.

    Dev Cell   Vol. 20 ( 2 ) page: 219-232   2011.2

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    DOI: 10.1016/j.devcel.2011.02.001

  32. Crooked, Coiled and Crimpled are three Ly6-like proteins required for proper localization of septate junction components Reviewed

    Nilton, A, Oshima, K, Zare, F, Byri, S, Nannmark, U, Nyberg, K G, Fehon, R G, and Uv, A E

    Development   Vol. 137 ( 14 ) page: 2427-2437   2010.6

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    DOI: 10.1242/dev.052605

  33. IKKε regulates F-actin assembly and interacts with Drosophila IAP1 in cellular morphogenesis Reviewed

    Oshima, K, Takeda, M, Kuranaga, E, Ueda, R, Aigaki, T, Miura, M, and Hayashi, S.

    Current Biology   Vol. 16 ( 15 ) page: 1531-1537   2006.8

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    DOI: 10.1016/j.cub.2006.06.032

  34. Weaning-induced expression of a milk-fat globule protein, MFG-E8, in mouse mammary glands, as demonstrated by the analyses of its mRNA, protein and phosphatidylserine-binding activity Reviewed

    Nakatani, H, Aoki, N, Nakagawa, Y, Jin-No, S, Aoyama, K, Oshima, K, Ohira, S, Sato, C, Nadano, D, Matsuda, T.

    Biochem J.   Vol. 395   page: 21-30   2006.4

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    DOI: 10.1042/BJ20051459

  35. Secretion of a peripheral membrane protein, MFG-E8, as a complex with membrane vesicles. Reviewed

    Oshima, Kenji and Aoki, Naohito and Kato, Takeo and Kitajima, Ken and Matsuda, Tsukasa

    European journal of biochemistry / FEBS   Vol. 269 ( 4 ) page: 1209--1218   2002

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    MFG-E8 (milk fat globule-EGF factor 8) is a peripheral membrane glycoprotein, which is expressed abundantly in lactating mammary glands and is secreted in association with fat globules. This protein consists of two-repeated EGF-like domains, a mucin-like domain and two-repeated discoidin-like domains (C-domains), and contains an integrin-binding motif (RGD sequence) in the EGF-like domain. To clarify the role of each domain on the peripheral association with the cell membrane, several domain-deletion mutants of MFG-E8 were expressed in COS-7 cells. The immunofluorescent staining of intracellular and cell-surface proteins and biochemical analyses of cell-surface-biotinylated and secreted proteins demonstrated that both of the two C-domains were required for the membrane association. During the course of these studies for domain functions, MFG-E8, but not C-domain deletion mutants, was shown to be secreted as membrane vesicle complexes. By size-exclusion chromatography and ultracentrifugation analyses, the complexes were characterized to have a high-molecular mass, low density and higher sedimentation velocity and to be detergent-sensitive. Not only such a exogenously expressed MFG-E8 but also that endogenously expressed in a mammary epithelial cell line, COMMA-1D, was secreted as the membrane vesicle-like complex. Scanning electron microscopic analyses revealed that MFG-E8 was secreted into the culture medium in association with small membrane vesicles with a size from 100 to 200 nm in diameter. Furthermore, the expression of MFG-E8 increased the number of these membrane vesicle secreted into the culture medium. These results suggest a possible role of MFG-E8 in the membrane vesicle secretion, such as budding or shedding of plasma membrane (microvesicles) and exocytosis of endocytic multivesicular bodies (exosomes).

  36. An ELISA-Based Assay for Detergent-solubilized Cellular .BETA.1,4-Galactosyltransferase Activity. Use of a Polyacrylamide Derivative with GlcNAc-.BETA. Side Chains as a Solid Phase Acceptor Substrate. Reviewed

    OUBIHI, Mohamed and Oshima, Kenji and Aoki, Naohito and KOBAYASHI, Kazukiyo and Kitajima, Ken and Matsuda, Tsukasa

    Bioscience, biotechnology, and biochemistry   Vol. 64 ( 4 ) page: 785--792   2000

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    ... Biochem., 64 (4), 785-792, 2000 M An ELISA - Based Assay for Detergent - solubilized Cellular {\ss

    DOI: 10.1271/bbb.64.785

  37. Lactation-dependent expression of an mRNA splice variant with an exon for a multiply O-glycosylated domain of mouse milk fat globule glycoprotein MFG-E8. Reviewed

    Oshima, K and Aoki, N and Negi, M and Kishi, M and Kitajima, K and Matsuda, T

    Biochemical and biophysical research communications   Vol. 254 ( 3 ) page: 522--528   1999

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    Expression of mRNA encoding MFG-E8, a milk fat-associated glycoprotein was investigated in mouse mammary gland. Two forms of mRNA, long and short variants, were shown to be expressed in the mammary tissue by RT-PCR analysis. Sequence analyses of these two variants and an isolated MFG-E8 gene segment indicated that the long and short mRNA variants resulted from an alternative splicing of a single pre-mRNA through in-flame inclusion and skipping of one exon, which encodes a proline/threonine (Pro/Thr)-rich domain. The long variant was expressed predominantly in mammary gland and the expression level was remarkably increased at late gestation and kept high during lactation. On the contrary, the short variant was detected ubiquitously in various tissues and its expression in the mammary gland was rather decreased in a lactation dependent manner. Expression of the long variant was also detected in a mouse mammary epithelial cell line, COMMA-1D, and enhanced by incubation with lactogenic hormones. Glycosylation inhibition analyses using tunicamycin and alpha-benzyl-GalNAc were conducted with COS7 cells transfected with plasmids expressing each mRNA variant, demonstrating that a fully glycosylated product of the long mRNA variant was not only N-glycosylated but also multiply O-glycosylated, whereas a product of the short one had only N-glycan(s). These results suggest that the alternative splicing plays a critical role for the mammary-specific and lactation-dependent expression of the MFG-E8 isoform and that the multiply O-glycosylated Pro/Thr-rich domain of this isoform is functionally important for formation of milk fat globules in mammary epithelial cells.

    DOI: 10.1006/bbrc.1998.0107

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Books 1

  1. MFG-E8: Origin, Structure, Expression, Functions and Regulation

    Kenzi Oshima, Takehiko Yasueda, Shunsuke Nishio and Tsukasa Matsuda( Role: Joint author)

    Springer Netherlands  2014.3  ( ISBN:978-94-017-8765-9

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    Language:English

KAKENHI (Grants-in-Aid for Scientific Research) 3

  1. 離乳期特異的な腸管IgA産生誘導が腸内細菌叢の長期制御に与える影響の解析

    Grant number:24K08806  2024.4 - 2027.3

    科学研究費助成事業  基盤研究(C)

    大島 健司

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    Authorship:Principal investigator 

    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

    腸内細菌叢は宿主の健康状態と密接に関連することが分かってきているが、腸内細菌叢は個人ごとに異なっている。健全な腸内細菌叢を形成、維持するには、個人差の形成メカニズムを理解することが重要である。そこで申請者は、腸内細菌叢の個人差を形成する因子のひとつとして腸管IgAについて着目した。大人型腸内細菌叢の定着とIgA産生はどちらも離乳期に開始されるため、本研究では離乳期に形成される腸管IgA抗原認識部位の多様性(IgAレパートリー)が腸内細菌叢の個人差形成に重要であると仮説を立て、マウスを用いた実験系によりその重要性について解析する。

  2. 乳児期から離乳期の腸内環境に応じた代謝・免疫の長期持続調節の解析

    Grant number:21K05455  2021.4 - 2025.3

    科学研究費助成事業  基盤研究(C)

    大島 健司

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    胎児期から離乳期にかけての栄養状態は、成人後の免疫系や代謝系にまで影響を与える。 その原因として、極端な栄養による初期発生時のストレス応答に加え、乳幼児期で確立する 栄養環境への長期的な適応が影響すると考えられている。乳幼児期で低栄養を経験した後に 高カロリー食を続けるなど栄養環境の適応がミスマッチすると、代謝疾患などの非感染性疾患のリスクとなることが明らかとされているため、この調節が正しく行われることで生涯の疾患リスクを減らすことが期待出来る。本研究では、腸内環境に応じた乳児期から離乳期にかけての生理機能調節に関連した、乳成分や腸内細菌に対する腸管組織の応答を解析する。
    乳児期から離乳期にかけての腸内細菌叢バランスや栄養状態は、免疫系や代謝系の制御機構に影響し、共生微生物に対する過剰な免疫応答の抑制や、飢餓的な栄養環境への適応といった長期的な個体の免疫・代謝制御に関与することが知られている。乳幼児期の栄養不足または過剰摂取は、代謝疾患などの非感染性疾患のリスクとなることが明らかとされており、乳幼児栄養による適応調節が正しく行われることで生涯の疾患リスクを減らすことが期待出来る。乳児栄養による栄養補給に加え、母乳に含まれる乳タンパク質は様々な生理機能を持ち、腸管組織や免疫系の発達・成熟に重要であることが多くの研究により報告されている。そのため世界保健機関などにより、ヒトでは離乳を開始する生後6ヶ月までは、母乳による乳児哺育が推奨されている。しかしながら、未だ母乳成分が生体に及ぼす作用は完全には明らかとなっていないため、母乳栄養の代わりとなる人工乳の利用について、将来的な非感染性疾患のリスク評価と対策を完全に行うことができていない。また栄養源が母乳から通常食に切り替わる離乳期では、腸内細菌が消化管内で急激に増殖・定着し、菌体成分や代謝産物が宿主の免疫系や代謝系へと影響する。本研究では、乳児期から離乳期にかけての腸内環境に応じた生理機能調節について、母乳成分が乳児腸上皮細胞に作用する機構と、離乳期の食物で形成される腸内細菌叢による長期的な代謝制御や免疫制御について焦点を当てて解析を行う。
    2023年度は、離乳期の腸内細菌叢形成の撹乱が、長期的な腸内細菌叢形成に影響をおよぼす可能性とその機序について重点的に解析を行った。また母乳成分である機能性乳タンパク質ラクトフェリン(LF)の消化管における作用機序の解析を行なった。
    2023年度は、離乳期の腸内細菌叢形成の撹乱が、長期的な腸内細菌叢形成に影響をおよぼす可能性とその機序について重点的に解析を行った。離乳期は、母乳から通常食へと切り替わる時期であり、これにより乳幼児が初めて出会う腸内細菌が消化管内で急激に増殖・定着し、免疫系の活性化が誘導される。近年、腸内細菌により誘導される離乳期に限定的な長期免疫調節機構が存在することが明らかになりつつある。これまでに、離乳期の腸内細菌叢形成を撹乱するため、離乳前後の2週間抗生物質を投与し、長期間の腸内細菌叢形成に影響を与えるか解析したところ、8週齢で数種類の腸内細菌の定着量に影響が見られた。長期的な菌叢の制御に関連する宿主側因子として、腸管管腔へ分泌されるIgAに着目し、可変領域配列のバリエーション(IgAレパートリー)を解析した。その結果、離乳期抗生物質処理によりIgAレパートリーが影響されることを明らかとした。
    また、母乳中の機能性タンパク質であるLFの消化管における生理機能の解析を行なった。LFは食餌性脂肪の吸収と代謝に影響することが報告されているが、経口摂取したLFが消化管での脂肪吸収にどのような作用を持つか明らかとなっていない。これまでに、マウスおよび培養細胞を用いた解析で、LFは腸管組織から血中への脂質吸収を抑制することを示唆する結果を得ている。LFの生理活性を明らかにするため、成獣マウスで脂質吸収抑制について再現性を確認し、胃内でのLF消化によりこの活性が失われることを明らかにした。
    以上から、研究課題はおおむね計画通りに進展したが、論文化の作業が完了していないため、次年度に予算を繰越すこことした。
    2024年度は、これまでに得られた実験結果の論文投稿準備を行い、発表のための追加実験を実施する。

  3. Interaction of sperm protease with egg extracellular matrix and its application to reproduction technology

    Grant number:20H02949  2020.4 - 2024.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Matsuda Tsukasa

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    Authorship:Coinvestigator(s) 

    Mammalian egg cells are coated with an egg-specific extracellular matrix (zona pellucida, ZP), and ZP plays an important role in sperm-egg interactions during fertilization. Sperm acrosin (ACR) functions as a protease that specifically degrades ZP component proteins.
    The degradation of recombinant ZP proteins by active recombinant ACR was investigated in human and pigs with different ZP constituent proteins. In both pig and human, ACR was found to cleave and fragment ZP proteins at specific sites. Human ACR was less active in fragmenting porcine ZP protein, suggesting the existence of species specificity in the degradation of oocyte membrane ZP protein by sperm ACR.

 

Teaching Experience (On-campus) 20

  1. Food Hygiene and Safety

    2024

  2. 修士論文研究1

    2024

  3. 生命農学演習4

    2024

  4. 生命農学演習1

    2021

  5. Food Hygiene and Safety

    2020

  6. 生命農学演習1

    2020

  7. 情報リテラシー入門

    2020

  8. 食品衛生学

    2019

  9. 応用生命科学実験実習1

    2019

  10. 分子細胞生物学特論2

    2019

  11. 分子細胞生物学特論2

    2018

  12. 応用生命科学実験実習1

    2018

  13. 応用生命化学特論II

    2017

  14. 応用生命科学実験実習1

    2017

  15. 応用生命科学実験実習1

    2016

  16. 応用生命化学特論II

    2016

  17. 応用生命化学特論II

    2015

  18. 応用生命科学実験実習1

    2015

  19. 応用生命化学特論IV

    2014

  20. 応用生命科学実験実習1

    2014

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