Molecular and functional analysis of bioactive factor AGF in biological control system

• Project/Area Number: 22790111
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Drug development chemistry
• Research Institution: Kumamoto University
• Principal Investigator: MIYATA Keishi 熊本大学, 大学院・生命科学研究部, 特任准教授 (50398228)
• 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: 生理活性 / メタボリックシンドローム / アンジオポエチン様因子

Research Abstract

We investigated the function of angiopoietin-related growth factor(AGF) using AGF transgenic mice. AGF regulates enhancing of energy metabolism in a manner independent of its proangiogenic function in brown adipose tissue and skeletal muscle. Furthermore, to examine short cold-induced thermogenesis and treadmill exercise, we found that AGF transgenic mice performed significantly more work in treadmill exercise and a significantly less decline in body temperature at cold-induced thermogenesis than the wild-type control mice. Taken together, we suggested that AGF upregulates not only energy metabolism but also exercise capacity and the prevention of hypothermia.

Research Products

• [Journal Article] Macrophage-derived angiopoietin-like protein 2 accelerates development of abdominal aortic aneurysm (2012)
  • Author(s): Tazume H, Miyata K, Tian Z, Endo M, Horiguchi H, Takahashi O, Horio E, Tsukano H, Kadomatsu T, Nakashima Y, Kunitomo R, Kaneko Y, Moriyama S, Sakaguchi H, Okamoto K, Hara M, Yoshinaga T, Yoshimura K, Aoki H, Araki K, Hao H, Kawasuji M, Oike Y.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32(6) Pages: 1400-9
  • Peer Reviewed
• [Journal Article] Synthesis and Biological Evaluation of Derivatives of 2-{2-Fluoro-4-[(2-oxocyclopentyl) methyl] phenyl} propanoic Acid : Nonsteroidal Anti-Inflammatory Drugs with Low Gastric Ulcerogenic Activity (2012)
  • Author(s): Yamakawa N, Suemasu S, Okamoto Y, Tanaka KI, Ishihara T, Asano T, Miyata K, Otsuka M, Mizushima T.
  • Journal Title: J Med Chem Volume: (in press)
• [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, Mochizuki N, Iwase H, Oike Y.
  • Journal Title: Cancer Res Volume: 72(7) Pages: 1784-84
  • 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(3) Pages: 494-9
  • Peer Reviewed
• [Journal Article] Genetic variants at the 9p21 locus contribute to atherosclerosis through modulation of ANRIL and CDKN2A/B (2012)
  • Author(s): Congrains A, Kamide K, Oguro R, Yasuda O, Miyata K, Yamamoto E, Kawai T, Kusunoki H, Yamamoto H, Takeya Y, Yamamoto K, Onishi M, Sugimoto K, Katsuya T, Awata N, Ikebe K, Gondo Y, Oike Y, Ohishi M, Rakugi H.
  • Journal Title: Atherosclerosis Volume: 220(2) Pages: 449-55
  • Peer Reviewed
• [Journal Article] Targeted overexpression of Angptl6/angiopoietin-related growth factor in the skin promotes angiogenesis and lymphatic vessel enlargement in response to ultraviolet B (2012)
  • Author(s): Okazaki H, Hirakawa S, Shudou M, Nakaoka Y, Shirakata Y, Miyata K, Oike Y, Hashimoto K, Sayama K.
  • Journal Title: J Dermatol Volume: 39(4) Pages: 366-74
  • NAID: 10031184909
  • Peer Reviewed
• [Journal Article] アンジオポエチン様因子 (2012)
  • Author(s): 宮田敬士, 尾池雄一
  • Journal Title: Vascular Medicine Volume: 8巻 Pages: 61-66
• [Journal Article] Synthesis and biological evaluation of derivatives of 2-{2-fluor)-4-[(2-oxocyclopentyl) methyl] phenyl } propanoic acid : Non-steroidal Anti-inflammatory Drugs with Low Gastric Ulcerogenic Activity (2012)
  • Author(s): NAOKI YAMAKAWA, Shintaro Suemasu, Yoshinari Okamoto, Ken-ichiro Tanaka, Tomoaki Ishihara, Teita Asano, Keishi Miyata, Masami Otsuka, Tohru Mizushima
  • Journal Title: Journal of Medicinal Chemistry Volume: (in press) Issue: 11 Pages: 3299-3311
  • DOI: 10.1021/jm300049g
  • Peer Reviewed
• [Journal Article] Genetic variants at the 9p21 locus contribute to a atherosclerosis through modulation of ANRIL and CDKN2A/B (2012)
  • Author(s): Congrains, A.(共著)
  • Journal Title: Atherosclerosis Volume: 220 Issue: 2 Pages: 449-455
  • DOI: 10.1016/j.atherosclerosis.2011.11.017
  • Peer Reviewed
• [Journal Article] The role of angiopoietin-like protein 2 in pathogenesis of dermatomyositis (2012)
  • Author(s): Ogata A, et al
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 418 Issue: 3 Pages: 494-499
  • DOI: 10.1016/j.bbrc.2012.01.052
  • Peer Reviewed
• [Journal Article] Targeted overexpression of Angpt16/angiopoietin-related growth factor in the skin promotes angiogenesis and lymphatic vessel enlargement in response to ultraviolet B (2012)
  • Author(s): Okazaki H, et al
  • Journal Title: J Dermatol Volume: 39 Issue: 4 Pages: 366-74
  • DOI: 10.1111/j.1346-8138.2011.01396.x
  • Peer Reviewed
• [Journal Article] A critical role for tumor cell-derived angiopoientin-like protein 2 in metastasis (2012)
  • Author(s): Endo M, et al
  • Journal Title: Cancer Research Volume: (in press) Issue: 7 Pages: 1784-1794
  • DOI: 10.1158/0008-5472.can-11-3878
  • Peer Reviewed
• [Journal Article] Macrophage-derived Angiopoietin-like Protein 2 Accelerates Development of Abdominal Aortic Aneurysms (2012)
  • Author(s): Tazume H, et al
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] アンジオポエチン様因子 (2012)
  • Author(s): 宮田敬士
  • Journal Title: Vascular Medicine Volume: 8 Pages: 61-66
• [Journal Article] Angiopoietin-like protein 2 is an important facilitator of inflammatory carcinogenesis and 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(24) Pages: 7502-12
  • Peer Reviewed
• [Journal Article] Nifedipine increases energy expenditure by increasing PGC-1α expression in skeletal muscle (2011)
  • Author(s): Tian Z, Miyata K, Tabata M, Yano M, Tazume H, Aoi J, Takahashi O, Araki K, Kawasuji M, Oike Y.
  • Journal Title: Hypertens Res Volume: 34(11) Pages: 1221-7
  • NAID: 10030277511
  • Peer Reviewed
• [Journal Article] Synthesis and biological evaluation of loxoprofen derivatives (2011)
  • Author(s): Yamakawa N, Suemasu S, Matoyama M, Tanaka K, Katsu T, Miyata K, Okamoto Y, Otsuka M, Mizushima T.
  • Journal Title: Bioorg Med Chem Volume: 19(11) Pages: 3299-311
  • Peer Reviewed
• [Journal Article] Angptlファミリー (2011)
  • Author(s): 宮田敬士, 尾池雄一
  • Journal Title: 日本臨牀 Volume: 69巻(増刊) Pages: 319-324
• [Journal Article] Angptlファミリーとメタボリックシンドローム (2011)
  • Author(s): 宮田敬士, 尾池雄一
  • Journal Title: Annual Review糖尿病・代謝・内分泌2011 Pages: 19-207
• [Journal Article] Angipoietin関連因子 (2011)
  • Author(s): 宮田敬士, 尾池雄一
  • Journal Title: 心臓 Volume: 43巻 Pages: 610-614
• [Journal Article] Nifedipine Increases Energy Expenditure by Increasing PGC-1α Expression in Skeletal Muscle (2011)
  • Author(s): Tian Z, Miyata K, et al
  • Journal Title: Hypertension Research Volume: 34 Issue: 11 Pages: 1221-1227
  • DOI: 10.1038/hr.2011.129
  • NAID: 10030277511
  • Peer Reviewed
• [Journal Article] Angiopoietin-like protein 2 is an important facilitator of inflammatory carcinogenesis and metastasis (2011)
  • Author(s): Aoi J, et al
  • Journal Title: Cancer Research Volume: 71 Issue: 24 Pages: 7502-7512
  • DOI: 10.1158/0008-5472.can-11-1758
  • Peer Reviewed
• [Journal Article] Angiopoietin関連因子 (2011)
  • Author(s): 宮田敬士
  • Journal Title: 心臓 Volume: 43 Pages: 610-614
• [Journal Article] Angptlファミリー (2011)
  • Author(s): 宮田敬士
  • Journal Title: 日本臨牀(増刊) Volume: 69 Pages: 319-324
• [Journal Article] Angptlファミリーとメタボリックシンドローム (2011)
  • Author(s): 宮田敬士
  • Journal Title: Annual Review糖尿病・代謝・内分泌2011 Pages: 199-207
• [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(10) Pages: 1925-32
  • Peer Reviewed
• [Journal Article] Macrophage-derived AIM is endocytosed into adipocytes and decreases lipid droplets via inhibition of fatty acid synthase activity (2010)
  • Author(s): Kurokawa J, Arai S, Nakashima K, Nagano H, Nishijima A, Miyata K, Ose R, Mori M, Kubota N, Kadowaki T, Oike Y, Koga H, Febbraio M, Iwanaga T, Miyazaki T.
  • Journal Title: Cell Metab Volume: 11(6) Pages: 479-92
  • 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(5) Pages: 2309-19
  • Peer Reviewed
• [Journal Article] Increased E4 activity in mice leads to ubiquitin-containing aggregates and degeneration of hypothalamic neurons resulting in obesity (2010)
  • Author(s): Susaki E, Kaneko-Oshikawa C, Miyata K, Tabata M, Yamada T, Oike Y, Katagiri H, Nakayama KI.
  • Journal Title: J Biol Chem Volume: 285(20) Pages: 15538-47
  • Peer Reviewed
• [Journal Article] 病態におけるアンジオポエチン様因子ファミリーの役割 (2010)
  • Author(s): 宮田敬士, 尾池雄一
  • Journal Title: 実験医学 Volume: 28巻(増刊) Pages: 1693-1697
• [Journal Article] 病態におけるアンジオポエチン様因子ファミリーの役割 (2010)
  • Author(s): 宮田敬士
  • Journal Title: 実験医学(増刊) Volume: 28 Pages: 1693-1697
• [Presentation] Angiopoietin-Related Growt h Factor(AGF) Regulates Energy Meta bolism in a Manner Independent of i ts Proangiogenic Function (2012)
  • Author(s): 宮田敬士
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡国際会議場(福岡)
  • Year and Date: 2012-03-16
• [Presentation] Angiopoietin-Related Growth Factor (AGF) Regulates Energy Metabolism in a Manner Independent of its Proangiogenic Function (2012)
  • Author(s): 宮田敬士
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡県福岡市福岡国際会議場
  • Year and Date: 2012-03-16
• [Presentation] Angiopoietin-related Growt h Factor Has the Anti-obesity Effect through eNOS-independent Pathway (2011)
  • Author(s): 宮田敬士
  • 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)
  • Year and Date: 2011-12-14
• [Presentation] Angiopoietin-related Growth Factor Has the Anti-obesity Effect through eNOS-independent Pathway (2011)
  • Author(s): 宮田敬士
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 神奈川県横浜市パシフィコ横浜
  • Year and Date: 2011-12-14
• [Presentation] Angptl6/AGF Regulates Ener gy Metabolism in a Manner Independent of its Proangiogenic Function (2010)
  • Author(s): 宮田敬士
  • 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
  • Place of Presentation: 神戸ポートアイランド(兵庫)
  • Year and Date: 2010-12-10
• [Presentation] Angptl6/AGF Regulates Energy Metabolism in a Manner Independent of its Proangiogenic Function (2010)
  • Author(s): 宮田敬士
  • 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
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2010-12-10