Role of adipokines and inflammatory cytokines in the regulation of the mammary gland development and the pathogenesis of mastitis and breast cancer

• Project/Area Number: 18380172
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Basic veterinary science/Basic zootechnical science
• Research Institution: Hokkaido University
• Principal Investigator: KIMURA Kazuhiro Hokkaido University, 大学院・獣医学研究科, 教授 (30192561)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥15,000,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥2,400,000); Fiscal Year 2008: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2007: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2006: ¥4,600,000 (Direct Cost: ¥4,600,000)
• Keywords: 乳腺 / 乳房炎 / 乳癌 / 脂肪細胞 / 肥満 / サイトカイン / レプチン / HGF / heregulin / 上皮間質相互作用 / 間質脂肪細胞 / 性ホルモン / 性ホルモンン / 乳腺上皮 / 形態形成 / カスパーゼ1 Caspase1 / マクロファージ

Research Abstract

未妊娠の雌マウスにおいて肥満が乳腺発達異常(導管径の短縮と分岐数の減少、筋上皮細胞層の欠失とコラーゲン層の肥厚)をもたらすことを明らかにし、その異常の一部は脂肪細胞分泌因子レプチンに因ることを強く示唆した。一方、イヌ乳腺腫瘍組織より得た不死化細胞5株の増殖はレプチンにより影響されず、癌化に伴う応答性の変化が示唆された。さらに導管形成を促進する成長因子HGFの脂肪細胞における発現調節機構などについて検討した。

Research Products

• [Journal Article] Diet-induced obesity disruptsductal development in the mammaryglands of nonpregnant mice (2009)
  • Author(s): Kamikawa, A., Ichii, O., Yamaji, D.,Imao, T., Suzuki, C., Okamatsu-Ogura, Y., Terao, A., Kon, Y. and Kimura, K.
  • Journal Title: Dev. Dyn 238 Pages: 1092-1099
  • Peer Reviewed
• [Journal Article] Diet-induced obesity disrupts ductal development in the mammary glands of nonpregnant mice (2009)
  • Author(s): Kamikawa, A., et.al.
  • Journal Title: Dev. Dyn. (印刷中)
  • Peer Reviewed
• [Journal Article] Role of uncoupling protein 1 in the anti-obesity effect ofs3-adrenergic agonist in the dog (2008)
  • Author(s): Omachi, A., Matsushita, Y., Kimura, K. and Saito, M.
  • Journal Title: Res. Vet. Sci 85 Pages: 214-219
  • Peer Reviewed
• [Journal Article] Leptin inhibitsmitogen-induced proliferation ofperipheral T lymphocytes from Holsteincows (2008)
  • Author(s): Ahmed, M., Kimura, K., Soliman, M., Yamaji, D., Ishioka, K., Hagiwara, K. and Saito, M.
  • Journal Title: Vet .J 176 Pages: 361-368
  • Peer Reviewed
• [Journal Article] Geldanamycin enhances hepatocyte growth factor stimulationof eNOS phosphorylation in endothelialcells (2008)
  • Author(s): Makondo, K., Kamikawa, A., Ahmed, M.,Terao, A., Saito, M. and Kimura, K.
  • Journal Title: Eur. J. Pharmacol 582 Pages: 110-115
  • Peer Reviewed
• [Journal Article] FSP27 contributes to efficientenergy storage in murine whiteadipocytes by promoting the formationof unilocular lipid droplets (2008)
  • Author(s): Nishino, N., Tamori, Y., 他25名
  • Journal Title: J. Clin. Invest 118 Pages: 2808-2821
  • Peer Reviewed
• [Journal Article] 減量による肥満犬の糖代謝機能の改善 (2008)
  • Author(s): 大町麻子、石岡克己、寺尾晶、木村和弘
  • Journal Title: ペット栄養学会誌 11 Pages: 13-19
  • NAID: 130004625920
  • Peer Reviewed
• [Journal Article] FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets (2008)
  • Author(s): Nishino, N., et.al.
  • Journal Title: J. Clin. Invest. 118 Pages: 2808-2821
  • Peer Reviewed
• [Journal Article] Leptin inhibits mitogen-induced proliferation of peripheral T lymphocytes from Holstein cows (2008)
  • Author(s): Ahmed, M., et.al.
  • Journal Title: Vet. J. 176 Pages: 361-368
  • Peer Reviewed
• [Journal Article] Plasma leptinconcentration in dogs: Effects of bodycondition score, age, gender and breeds (2007)
  • Author(s): Ishioka, K., Hosoya, K., Kitagawa, H.,Shibata, H., Honjoh, T., Kimura, K. and Saito, M.
  • Journal Title: Res. Vet. Sci 82 Pages: 11-15
  • Peer Reviewed
• [Journal Article] Effects of leptin and tumornecrosis factor-α on degranulation andsuperoxide production ofpolymorphonuclear neutrophils fromHolstein cows (2007)
  • Author(s): Ahmed, M., Kimura, K., Soliman, M.,Yamaji, D., Okamatsu-Ogura, Y.,Makondo, K., Inanami, O. and Saito, M.
  • Journal Title: J. Vet. Med. ScI 69 Pages: 125-131
  • Peer Reviewed
• [Journal Article] Induction of proinflammatory cytokinesand caspase-1 by leptin inmonocyte/macrophages from Holsteincows (2007)
  • Author(s): Ahmed, M., Shaban, Z., Yamaji, D., Okamatsu-Ogura, Y., Soliman, M., AbdEldaim, M., Ishioka, K., Makondo, K., Saito, M. and Kimura, K
  • Journal Title: J. Vet. Med. ScI 69 Pages: 509-514
  • Peer Reviewed
• [Journal Article] Inverse regulation of leptinmRNA expression by short- andlong-chain fatty acids in the culturedbovine adipocytes (2007)
  • Author(s): Soliman, M., Kimura, K., Ahmed, M., Yamaji, D., Matsushita, Y., Okamatsu-Ogura, Y., Makondo, K., Saito, M.
  • Journal Title: Domest. Anim. Endocrinol 33 Pages: 400-409
  • Peer Reviewed
• [Journal Article] Leptin inhibits hepatocytegrowth factor-induced ductalmorphogenesis of bovine mammaryepithelial cells (2007)
  • Author(s): Yamaji, D., Kamikawa, A., Soliman, M.M., Ito, T., Ahmed, M.M., Makondo, K., Watanabe, A., Saito, M. and Kimura, K.
  • Journal Title: Jpn. J. Vet. Res. 54 Pages: 183-189
  • Peer Reviewed
• [Journal Article] Brown fat UCP1 is not involved in the febrile andthermogenic responses to IL-1 ss in mice (2007)
  • Author(s): Okamatsu-Ogura, Y., Kitao, N., Kimura,K. and Saito, M.
  • Journal Title: Am. J. Physiol. Endocrinol. Metab 292
  • Peer Reviewed
• [Journal Article] Day-night difference in ss 3-adrenoceptor agonist-induced energyexpenditure: contribution of brown fatthermogenesis and physical activity (2007)
  • Author(s): Okamatsu-Ogura, Y., Uozumi, A., Kitao,N., Kimura, K. and Saito, M.
  • Journal Title: Obesity Res. Clin. Pract 1 Pages: 61-67
  • Peer Reviewed
• [Journal Article] Uncoupling protein 1contributes to fat-reducing effect ofleptin (2007)
  • Author(s): Okamatsu-Ogura, Y., Uozumi, A., Toda,C., Kimura, K., Yamashita, H. and Saito,M
  • Journal Title: Obesity Res. Clin. Pract 1 Pages: 233-241
  • Peer Reviewed
• [Journal Article] Molecular cloning and tissue distribution ofuncoupling protein 1 (UCP1) in PlateauPika (Ochotona dauurica) (2007)
  • Author(s): Kitao, N., Yahata, T., Matsumoto, T., Okamatsu-Ogura, Y., Omachi, A., Kimura,K. and Saito, M.
  • Journal Title: J. Vet. Med .Sci 69 Pages: 1065-1068
  • Peer Reviewed
• [Journal Article] Dmbx1 is essential inagouti-related protein action (2007)
  • Author(s): Fujimoto, W., Shiuchi, T., 他8名
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 15514-15519
  • Peer Reviewed
• [Journal Article] ss3-Adrenoceptor agonist AJ-9677 reduces body fat inobese beagles (2007)
  • Author(s): Omachi, A., Ishioka, K., Uozumi, A., Kamikawa, A., Toda, C., Kimura, K. and Saito, M.
  • Journal Title: Res. Vet. ScI 83 Pages: 5-11
  • Peer Reviewed
• [Journal Article] Inverse regulation of leptin mRNA expression by short-and long-chain fatty acids in the cultured bovine adipocytes. (2007)
  • Author(s): Sohiman, M., et. al.
  • Journal Title: Domest. Anim. Endocrinol. 33 Pages: 400-409
  • Peer Reviewed
• [Journal Article] Leptin inhibits hepatocyte growth factor-induced ductal morphogenesis of bovine mammary epithelial cells. (2007)
  • Author(s): Yamaji, D., et. al.
  • Journal Title: Jpn. J. Vet. Res. 54 Pages: 183-189
  • Peer Reviewed
• [Journal Article] Induction of proinflammatory cytokines and caspase-1 by leptin in monocyte/macrophages from Holstein cows. (2007)
  • Author(s): Ahmed, M., et. al.
  • Journal Title: J. Vet. Med. Sci. 69 Pages: 509-514
  • Peer Reviewed
• [Journal Article] Leptin inhibits hepatocyte growth factor-induced ductal morphogenesis of bovine mammary epithelial cells. (2007)
  • Author(s): Yamaji, D., et al.
  • Journal Title: Jpn. J. Vet. Res. 54・4 Pages: 183-189
• [Journal Article] Effect of leptin and tumor necrosis factor-α on degranulation and superoxide production of polymorphonuclear neutrophils from Holstein cows. (2007)
  • Author(s): Ahmed, M., et al.
  • Journal Title: J. Vet. Med. Sci. 69 Pages: 125-131
• [Journal Article] Induction of proinflammatory cytokines and caspase-1 by leptin in monocyte/macrophages from Holstein cows. (2007)
  • Author(s): Ahmed, M., et al.
  • Journal Title: J. Vet. Med. Sci. 69 Pages: 513-518
• [Journal Article] Leptin inhibits mitogen-induced proliferation of peripheral T lymphocytes from Holstein cows. (2007)
  • Author(s): Ahmed, M., et al.
  • Journal Title: Vet. J. (印刷中)
• [Journal Article] Inverse regulation of leptin mRNA expression by short- and long-chain fatty acids in the cultured bovine adipocytes. (2007)
  • Author(s): Soliman, M., et al.
  • Journal Title: Domest. Anim. Endocrinol. (印刷中)
• [Journal Article] A novel phenotype of suppressing heat release contributes to homeothermic regulationin UCP1-deficient mice (2006)
  • Author(s): Wang, Y., Kimura, K., Saito, M., Kontani, Y., Kobayashi, Y., Mori, N. and Yamashita, H.
  • Journal Title: Pflugers Archiv-Eur. J. Physiol 452 Pages: 363-369
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor and c-Metsystems in bovine mammary gland (2006)
  • Author(s): Yamaji, D., Kimura, K., Watanabe, A.,Soliman, M., Ahamed, M., Kon, Y.,Iwanaga, T. and Saito, M.
  • Journal Title: Domest. Anim. Endocrinol 30 Pages: 239-246
  • Peer Reviewed
• [Journal Article] Canine adiponectin : cDNA structure, mRNA expression inadipose tissues and reduced plasmalevels in obesity (2006)
  • Author(s): Ishioka, K., Omachi, A., Sagawa, M., Shibata, H., Honjoh, T., Kimura, K. and Saito, M.
  • Journal Title: Res. Vet. ScI 80 Pages: 127-132
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor and c-Met systems in bovine mammary gland. (2006)
  • Author(s): Yamaji, D., et al.
  • Journal Title: Domest. Anim. Endocrinol. 30 Pages: 239-246
• [Presentation] アディポネクチンと生理活性因子の結合 : その特性と生理機能の阻害 (2008)
  • Author(s): 木村和弘、大倉有生、今尾武士、上川昭博、石井辰矢、岡松優子、寺尾晶
  • Organizer: 第13回アディポサイエンス研究会シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2008-08-22
• [Presentation] アディポネクチンと生理活性因子の結合特性 (2008)
  • Author(s): 木村和弘、大倉有生、今尾武士、上川昭博、石井辰矢、岡松優子、寺尾晶
  • Organizer: 第29回日本肥満学会
  • Place of Presentation: 大分
• [Presentation] 食事性肥満が乳腺導管の発達に及ぼす影響 (2008)
  • Author(s): 上川昭博、岡松優子、寺尾晶、木村和弘
  • Organizer: 第29回日本肥満学会
  • Place of Presentation: 大分
• [Presentation] 白色脂肪でのUCP1発現はレプチン感受性を増強させる (2008)
  • Author(s): 岡松優子、米代武司、寺尾晶、木村和弘
  • Organizer: 第29回日本肥満学会
  • Place of Presentation: 大分
• [Presentation] 脂肪細胞分泌因子アディポネクチンによる神経成長因子NGF の機能阻害 (2008)
  • Author(s): 木村和弘、大倉有生、今尾武士、上川昭博、石井辰矢、岡松優子、寺尾晶
  • Organizer: 第146回日本獣医学会学術集会
  • Place of Presentation: 宮崎
• [Presentation] 肥満犬の減量に伴う栄養代謝因子の変化とインスリン抵抗性の改善 (2007)
  • Author(s): 大町麻子、石岡克己、寺尾晶、木村和弘
  • Organizer: 第4回日本獣医内科学アカデミー学術大会(ペット栄養学会)
  • Place of Presentation: 東京
  • Year and Date: 2007-08-12
• [Presentation] レプチンの摂食抑制作用における脱共役蛋白質UCP1の役割 (2007)
  • Author(s): 岡松優子、木村和弘、渡辺久美子、松下真美、斉藤昌之
  • Organizer: 第28回日本肥満学会
  • Place of Presentation: 東京
• [Presentation] 脂肪細胞分泌因子アディポネクチンと神経成長因子NGF の相互作用 (2007)
  • Author(s): 大倉有生、春山貴志、寺尾晶、木村和弘
  • Organizer: 第28回日本肥満学会
  • Place of Presentation: 東京
• [Presentation] エストロジェンによる脂肪細胞由来細胞増殖因子HGF およびHRGαの遺伝子発現調節の遺伝子発現調節 (2007)
  • Author(s): 伊藤智樹、山地大介、上川昭博、寺尾晶、木村和弘
  • Organizer: 第144回日本獣医学会学術集会
  • Place of Presentation: 江別
• [Presentation] 脂肪細胞分泌因子レプチンの乳腺導管形成抑制作用 (2007)
  • Author(s): 上川昭博、山地大介、伊藤智樹、今尾武士、寺尾晶、木村和弘
  • Organizer: 第144回日本獣医学会学術集会
  • Place of Presentation: 江別
• [Presentation] Minor role of brown fatthermogenesis in IL-1 beta-inducedfever (2007)
  • Author(s): Okamatsu-Ogura, Y., Kitao, N., Kimura,K., Saito, M.
  • Organizer: 15th European congress on obesity
  • Place of Presentation: Hungary
• [Presentation] 乳腺上皮細胞の形態形成における間質脂肪細胞の役割 (2006)
  • Author(s): 木村和弘
  • Organizer: 第43回日本生化学会北海道支部例会
  • Place of Presentation: 札幌
  • Year and Date: 2006-11-03
• [Presentation] ウシ肝細胞増殖因子HGFの発現とその機能 (2006)
  • Author(s): 木村和弘、山地大介、マコンドケネディ、斉藤昌之
  • Organizer: 動物サイトカイン研究会第4回学術集会
  • Place of Presentation: 山口
  • Year and Date: 2006-09-24
• [Presentation] Species-Dependent Regulation of HGF Expression in Adipocytes Links the Morphogenic. Differentiation of MammaryEpithelial Cells (2006)
  • Author(s): Yamaji, D., Kimura, K., Watanabe, A., Kamikawa, A., Soliman, M.M., Saito, M.
  • Organizer: 第11回アディポサイエンス研究会シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2006-09-18
• [Presentation] 脂肪細胞由来分泌因子の乳腺組織構築における動物種差 (2006)
  • Author(s): 山地大介、木村和弘、渡部淳、上川昭博、Mohamed Soliman、斉藤昌之
  • Organizer: 第27回日本肥満学会
  • Place of Presentation: 大阪
• [Presentation] ss-Adrenergically controlled energymetabolism in brown adipose tissue (2006)
  • Author(s): Saito, M., okamatsu-Ogura, Y., Inokuma,K., Omachi, A., Kimura, K.
  • Organizer: 第27回日本肥満学会
  • Place of Presentation: 兵庫
• [Presentation] Effect of leptin on degranulation and superoxide productionof polymorphonuclear nuetrophils from Holstein cows (2006)
  • Author(s): Mohamed Ahmed、山地大介、岡松優子、Kennedy Makondo、稲波修、斉藤昌之、木村和弘
  • Organizer: 第142回日本獣医学会学術集会
  • Place of Presentation: 山口
• [Presentation] Role of adipocytes in the regulation of morphogenic diffentiationof bovine mammary epithelial cells (2006)
  • Author(s): Yamaji, D., Kimura,K., Soliman, M,M., Saito, M
  • Organizer: 10th International Congress on Obesity
  • Place of Presentation: Australia
• [Presentation] Adipocyte secreting factors control morphogenic differentiation ofbovine mammary epithelial cells. 20th IUBMB International congress of Biochemistry and Molecular Biology and11th. FAOBMB Congress (2006)
  • Author(s): Yamaji, D., Kimura, K., Watanabe, A., Soliman, M.M., Ahmed, M. M., Makondo, K., Saito, M
  • Organizer: 第20回国際生化学・分子生物学会議
  • Place of Presentation: 京都
• [Book] レプチン(SectionI-E-4-g)、ホルモンハンドブック 新訂eBook版 (2007)
  • Author(s): 木村和弘
  • Publisher: 日本比較内分泌学会編、南江堂
• [Remarks]
  • URL: http://www.vetmed.hokudai.ac.jp/biochemistry01.html