Analyses of the transcriptional regulatory mechanisms of chronic inflammation-related factor Angptl2

• Project/Area Number: 22790322
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Kumamoto University
• Principal Investigator: KADOMATSU Tsuyoshi 熊本大学, 大学院・生命科学研究部, 助教 (90555757)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 分子病態学 / Angpt12 / 転写調節 / 概日リズム / 時計遺伝子 / 慢性炎症

Research Abstract

In this study, we investigated the transcriptional regulatory mechanisms of Angptl2(angiopoietin-like protein 2) that plays roles in the pathogenesis and development of chronic inflammation-related diseases, such as metabolic syndrome or cancers. We showed that Angptl2 expression in cancer cells is synergistically activated by NFAT, ATF2, and c-Jun. Furthermore, we demonstrated that expression periodicity of Angptl2 in various tissues is regulated by a circadian clock and that disruption of this process resulted in the arrhythmic Angptl2 expression.

Research Products

• [Journal Article] Tumor cell-derived angiopoietin-like protein ANGPTL2 is a critical driver of metastasis (2012)
  • Author(s): Endo, M., Nakano, M., Kadomatsu, T., Fukuhara, S., Kuroda, H., Mikami, S., Hato, T., Aoi, J., Horiguchi, H., Miyata, K., Odagiri, H., Masuda, T., Harada, M., Horio, H., Hishima, T., Nomori, H., Ito, T., Yamamoto, Y., Minami, T., Okada, S., Takahashi, T.
  • Journal Title: Cancer Res Volume: 72 Pages: 1784-1794
  • Peer Reviewed
• [Journal Article] The role of angiopoietin-like protein 2 in pathogenesis of dermatomyositis (2012)
  • Author(s): Ogata, A., Endo, M., Aoi, J., Takahashi, O., Kadomatsu, T., Miyata, K., Tian, Z., Jinnin, M., Fukushima, S., Ihn, H., & Oike, Y.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 418 Pages: 494-499
  • Peer Reviewed
• [Journal Article] The role of angiopoietin-like protein 2 in pathogenesis of dermatomyositis (2012)
  • Author(s): Aki Ogata
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 418 Pages: 494-499
  • Peer Reviewed
• [Journal Article] The roles of angiopoietin-like protein 2 in carcinogenesis and tumor cell metastasis (2011)
  • Author(s): Aoi, J., Endo, M., Kadomatsu, T., Miyata, K., Nakano, M., Horiguchi, H., Ogata, A., Odagiri, H., Yano, M., Araki, K., Jinnin, M., Ito, T., Hirakawa, S., Ihn, H. & Oike, Y.
  • Journal Title: Cancer Res Volume: 71 Pages: 7502-7512
  • Peer Reviewed
• [Journal Article] Obesity resistance and increased hepatic expression of catabolism-related mRNAs in Cnot3(+/-) mice (2011)
  • Author(s): Morita, M., Oike, Y., Nagashima, T., Kadomatsu, T., Tabata, M., Suzuki, T., Nakamura, T., Yoshida, N., Okada, M. & Yamamoto, T.
  • Journal Title: EMBO J Volume: 30 Pages: 4678-4691
  • Peer Reviewed
• [Journal Article] Angiopoietin-like proteins : emerging targets for treatment of obesity and related metabolic diseases (2011)
  • Author(s): Kadomatsu, T., Tabata, M. & Oike, Y.
  • Journal Title: FEBS J Volume: 278 Pages: 559-564
  • Peer Reviewed
• [Journal Article] Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null mice (2011)
  • Author(s): Yano, M., Watanabe, K., Yamamoto, T., Ikeda, K., Senokuchi, T., Lu, M., Kadomatsu, T., Tsukano, H., Ikawa, M., Okabe, M., Yamaoka, S., Okazaki, T., Umehara, H., Gotoh, T., Song, WJ, Node, K., Taguchi, R., Yamagata, K. & Oike, Y.
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 3992-4002
  • NAID: 120006957387
  • Peer Reviewed
• [Journal Article] Angiopoietin-like protein 2 is an important facilitator of inflammatory carcinogenesis and metastasis (2011)
  • Author(s): Jun Aoi
  • Journal Title: Cancer Res Volume: 71 Pages: 7502-7512
  • Peer Reviewed
• [Journal Article] Angiopoietin-like proteins : emerging targets for treatment of obesity and related metabolic diseases (2011)
  • Author(s): Tsuyoshi Kadomatsu
  • Journal Title: FEBS Journal Volume: 278 Pages: 559-564
  • Peer Reviewed
• [Journal Article] The endoplasmic reticulum stress-C/EBP homologous protein pathway-mediated apoptosis in macrophages contributes to the instability of atherosclerotic plaques (2010)
  • Author(s): Tsukano, H., Gotoh, T., Endo, M., Miyata, K., Tazume, H., Kadomatsu, T., Yano, M., Iwawaki, T., Kohno, K., Araki, K., Mizuta, H. & Oike, Y.
  • Journal Title: Arterioscler. Thromb. Vasc. Biol Volume: 30 Pages: 1925-1932
  • Peer Reviewed
• [Journal Article] Synoviocyte-derived angiopoietin-like protein 2 contributes to synovial chronic inflammation in rheumatoid arthritis (2010)
  • Author(s): Okada, T., Tsukano, H., Endo, M., Tabata, M., Miyata, K., Kadomatsu, T., Miyashita, K., Semba, K., Nakamura, E., Tsukano, M., Mizuta, H. & Oike, Y.
  • Journal Title: Am. J. Pathol Volume: 176 Pages: 2309-2319
  • Peer Reviewed
• [Presentation] Circadian regulation of Angiopoietin-like protein 2 expression by a molecular clock (2011)
  • Author(s): 門松毅, 他
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-12-15
• [Presentation] Clock genes directly regulate the rhythmic Angptl2 expression. (2010)
  • Author(s): 門松毅, 他
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸国際展示場(神戸ポートアイランド・兵庫県)
  • Year and Date: 2010-12-07
• [Presentation] Clock genes directly regulate the rhythmic Angptl2 expression (2010)
  • Author(s): 門松毅
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会
  • Place of Presentation: 神戸国際展示場(神戸ポートアイランド・兵庫県)
  • Year and Date: 2010-12-07
• [Book] 実験医学増刊 (2011)
  • Author(s): 門松毅, 浦上将太, 尾池雄一
  • Publisher: 羊土社
• [Book] アンチ・エイジング医学 (2011)
  • Author(s): 門松毅, 尾池雄一
  • Publisher: メディカルレビュー社
• [Book] 実験医学増刊 (2011)
  • Author(s): 門松毅
  • Publisher: 羊土社
• [Book] アンチ・エイジング医学 (2011)
  • Author(s): 門松毅
  • Publisher: メディカルレビュー社
• [Book] 実験医学 (2010)
  • Author(s): 門松毅, 尾池雄一
  • Publisher: 羊土社
• [Book] 実験医学 (2010)
  • Author(s): 門松毅
  • Publisher: 羊土社
• [Remarks]
  • URL: http://molegene.kumamoto-u.ac.jp/