Roles of mammalian cold shock proteins in spermatogenesis

• Project/Area Number: 24592446
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Kyoto University
• Principal Investigator: FUJITA JUN 京都大学, 医学(系)研究科(研究院), 教授 (50173430)
• Co-Investigator(Renkei-kenkyūsha): NISHIYAMA Hiroyuki 筑波大学, 医学医療系, 教授 (20324642)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: ストレス応答 / 精巣 / 炎症 / 体内時計 / 発がん / ストレス / 細胞・組織

Outline of Final Research Achievements

To clarify the functions of the cold shock protein Cirp in vivo, we produced cirp-knockout mice. We found that Cirp facilitates proliferation of undifferentiated. spermatogonia by inhibiting Dyrk1b. Cirp confers robustness to circadian oscillators through regulation of Clock expression. CIRP functions extracellularly as well and is a damage-associated molecular pattern molecule that promotes inflammatory responses in shock and sepsis. Cirp promotes the development of inflammation and carcinogenesis in liver and colon through regulating apoptosis and production of cytokines in inflammatory cells.
Thus, Cirp has both beneficial and detrimental effects in vivo.

Research Products

• [Journal Article] Heat shock protein A4/Apg-2 is required for stem/progenitor cell maintenance in intestinal inflammation. (2015)
  • Author(s): Adachi T, Sakurai T, Kashida H, Mine H, Hagiwara S, Matsui S, Yoshida K, Nishida N, Watanabe T, Itoh K, Fujita J, Kudo M.
  • Journal Title: Inflammatory Bowel Disease Volume: 21 Issue: 1 Pages: 31-39
  • DOI: 10.1097/mib.0000000000000244
  • Peer Reviewed / Open Access
• [Journal Article] Cold-inducible RNA-binding protein (Cirp) promotes the development of liver cancer. (2015)
  • Author(s): Sakurai T, Yada N, Watanabe T, Arizumi T, Hagiwara S, Ueshima K, Nishida N, Fujita J, Kudo M.
  • Journal Title: Cancer Sci Volume: in press Issue: 4 Pages: 352-358
  • DOI: 10.1111/cas.12611
  • Peer Reviewed / Open Access
• [Journal Article] Heat shock protein A4 controls cell migration and gastric ulcer healing. (2015)
  • Author(s): Sakurai T, Kashida H, Hagiwara S, Nishida N, Watanabe T, Fujita J, Kudo M.
  • Journal Title: Dig Dis Sci. Volume: 60 Issue: 4 Pages: 850-857
  • DOI: 10.1007/s10620-015-3561-8
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Expression of the oncoprotein gankyrin and phosphorylated retinoblastoma protein in human testis and testicular germ cell tumor. (2014)
  • Author(s): Satoshi Ando, Taeko Matsuoka, Koji Kawai, Shintaro Sugita, Akira Joraku, Takahiro Kojima, Takahiro Suetomi, Jun Miyazaki, Jun Fujita and Hiroyuki Nishiyama
  • Journal Title: International Journal of Urology Volume: 21 Issue: 10 Pages: 992-998
  • DOI: 10.1111/iju.12484
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Stress response protein Cirp links inflammation and tumorigenesis in colitis-associated cancer. (2014)
  • Author(s): Sakurai T, Kashida H, Watanabe T, Hagiwara S, Mizushima T, Iijima H, Nishida N, Higashitsuji H, Fujita J, Kudo M.
  • Journal Title: Cancer Res Volume: 74 Issue: 21 Pages: 6119-6128
  • DOI: 10.1158/0008-5472.can-14-0471
  • Peer Reviewed / Open Access
• [Journal Article] Tumor necrosis factor and transforming growth factor beta regulate clock genes by controlling the expression of the cold inducible RNA - binding protein (CIRBP). (2014)
  • Author(s): Lopez MA, Meier D, Mueller AF, Franken P, Fujita J, Fontana A.
  • Journal Title: Journal of Biological Chemistry Volume: 289 Issue: 5 Pages: 2736-2744
  • DOI: 10.1074/jbc.m113.508200
  • Peer Reviewed
• [Journal Article] Risk factors for loss to follow-up during active surveillance of patients with Stage I seminoma. (2014)
  • Author(s): Endo T, Kawai K, Kamba T, Inai H, Uchida K, Miyazaki J, Kamoto T, Ogawa O, Nishiyama H.
  • Journal Title: Jpn J Clin Oncol. Volume: 44(4) Issue: 4 Pages: 355-359
  • DOI: 10.1093/jjco/hyu001
  • Peer Reviewed
• [Journal Article] Hypothermia protects against fulminant hepatitis in mice by reducing reactive oxygen species production. (2013)
  • Author(s): Sakurai T, Kudo M, Watanabe T, Itoh K, Higashitsuji H, Arizumi T, Inoue T, Hagiwara S, Ueshima K, Nishida N, Fukumoto M, Fujita J.
  • Journal Title: Dig Dis Volume: 31 Issue: 5-6 Pages: 440-6
  • DOI: 10.1159/000355242
  • Peer Reviewed
• [Journal Article] Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis. (2013)
  • Author(s): Qiang X*, Yang W-L, Wu R, Zhou M, Jacob A, Dong W, Kuncewitch M, Ji Y, Yang H, Wang H, Fujita J, Nicastro J, Coppa GF, Tracey KJ, Wang P.
  • Journal Title: Nature Medicine Volume: 19 Issue: 11 Pages: 1489-1495
  • DOI: 10.1038/nm.3368
  • Peer Reviewed
• [Journal Article] Overexpression of gankyrin in mouse hepatocytes induces hemangioma by suppressing factor inhibiting hypoxia-inducible factor-1 (FIH-1) and activating hypoxia-inducible factor-1 (2013)
  • Author(s): Y. Liu, H. Higashitsuji, K. Itoh, T. Sakurai, K. Koike, K. Hirota, M. Fukumoto, J. Fujita
  • Journal Title: Biochemical and biophysical research communications Volume: 432 Issue: 1 Pages: 22-27
  • DOI: 10.1016/j.bbrc.2013.01.093
  • Peer Reviewed
• [Journal Article] Cold-inducible RNA-binding protein (Cirp) interacts with Dyrk1b/Mirk and promotes proliferation of immature male germ cells in mice (2012)
  • Author(s): Masuda T, et al.
  • Journal Title: Proc Natl Acad Sci USA Volume: 109 Issue: 27 Pages: 10885-108901
  • DOI: 10.1073/pnas.1121524109
  • Peer Reviewed
• [Journal Article] Cold-inducible RNA-binding protein modulates circadian gene expression posttranscriptionally. (2012)
  • Author(s): Morf J, Rey G, Schneider K, Stratmann M, Fujita J, Naef F, Schibler U.
  • Journal Title: Science Volume: 338 Issue: 6105 Pages: 379-383
  • DOI: 10.1126/science.1217726
  • Peer Reviewed
• [Journal Article] Identification of a novel enhancer that binds Sp1 and contributes to induction of cold-inducible RNA-binding protein (cirp) expression in mammalian cells. (2012)
  • Author(s): Sumitomo Y, Higashitsuji H, Higashitsuji H, Liu Y, Fujita T, Sakurai T, et al
  • Journal Title: BMC Biotechnol Volume: 12 Issue: 1 Pages: 72-72
  • DOI: 10.1186/1472-6750-12-72
  • Peer Reviewed
• [Journal Article] In situ differentiation of CD8αα T cells from CD4 T cells in peripheral lymphoid tissues (2012)
  • Author(s): Nambu Y., Hayashi T., Jang KJ, Aoki K., Mano H., Nakano K., Osato M., Takabashi K., Itoh K., Teramukai S., Komon T., Fujita J., Ito Y., Shimizu
  • Journal Title: Scientific Reports Volume: 2 Issue: 1 Pages: 930-930
  • DOI: 10.1038/srep00642
  • Peer Reviewed
• [Presentation] ほ乳類低温ショックタンパク質Cirpは炎症反応を増悪させる (2014)
  • Author(s): 藤田潤
  • Organizer: 第9回臨床ストレス応答学会大会
  • Place of Presentation: 岡山市
  • Year and Date: 2014-11-01 – 2014-11-02
• [Presentation] 熱ショック蛋白質Apg-1 (Hspa4l/Osp94/HspH3)欠損によるマウス雄性不妊の機序 (2014)
  • Author(s): 藤田潤、伊藤克彦
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸市
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] 低温ショックタンパク質Cirpの生理的な機能の解析 (2013)
  • Author(s): 藤田潤
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: 札幌
• [Presentation] ほ乳類低温ショックタンパク質Cirpの生理機能 (2012)
  • Author(s): 藤田潤
  • Organizer: 臨床ストレス応答学会
  • Place of Presentation: 東京都