Molecular basis of anti-angiogenic barriers in mesenchymal tissues
| Project/Area Number |
17014046
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University |
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Principal Investigator |
HIRAKI Yuji Kyoto University, 再生医科学研究所, 教授 (40144498)
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| Co-Investigator(Kenkyū-buntansha) |
SHUKUNAMI Chisa 京都大学, 再生医科学研究所, 准教授 (60303905)
KONDO Shunya 京都大学, 再生医科学研究所, 助教 (80362523)
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| Project Period (FY) |
2005 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥45,400,000 (Direct Cost: ¥45,400,000)
Fiscal Year 2009: ¥8,700,000 (Direct Cost: ¥8,700,000)
Fiscal Year 2008: ¥8,700,000 (Direct Cost: ¥8,700,000)
Fiscal Year 2007: ¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 2006: ¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 2005: ¥8,400,000 (Direct Cost: ¥8,400,000)
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| Keywords | chondromodulin-I / VEGF / 血管侵入抵抗性 / 生体分子 / 結合組織 / tenomodulin / 組織・細胞 / 発生・分化 / 血管進入抵抗性 |
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| Research Abstract |
In general, mesenchymal tissues are well-vascularized and permissive to vascular invasion upon stimulation by proangiogenic stimuli. However, anti-angiogenic mesenchymes are also known in the body. Abnormal vascular invasion into these tissues is devastating to physiological functions in organs and often pathogenic. In this study, we investigate the molecular basis of anti-angiogenic properties of mesenchymal structures with special attention to tissue-specific angiogenesis inhibitors, chondromodulin-I (ChM-I) and tenomodulin (Tnmd). Our present results indicate that the angiogenic signal balance between VEGF-A vs. ChM-I/Tnmd underlies the control of tissue vascularity and vascular homeostasis. Moreover, we clearly demonstrated that the loss of these inhibitors plays an important pathogenic role in angiogenic diseases as well as the overexpression of angiogenic factors such as VEGF-A. In the meantime, we successfully expressed recombinant human ChM-I with a high specific activity compa
… More
rable to that of naturally occurring ChM-I. Using this preparation of recombinant protein, we have shown that ChM-I inhibits angiogenic actions of cultured vascular endothelial cells in response to VEGF-A through a unique mode of signaling pathway. Then, to gain a further insight into functions of anti-angiogenic barriers, we attempted to visualize anti-angiogenic barriers during endochondral bone formation by overexpressing VEGF-A with a viral vector in chick limb buds. Circulating microvessels were visualized by injecting India ink through the extraembryonic vitelline vein. VEGF-A thus expressed dramatically induced a high density of vasculature in connective tissue, which enabled us to identify perichondrial anti-angiogenic barriers surrounding cartilaginous bone rudiments for the first time. This novel anti-angiogenic barrier is regulated by a specific mode of VEGF-A signal reception and plays a central role in vascular invasion into cartilage to occur. These results will provide a important clue to the development of a novel anti-tumor therapy. Less
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Report
(6 results)
Research Products
(61 results)
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[Journal Article] Altered fracture callus formation in chondromodulin-I deficient mice.2008
Author(s)
K. Yukata, Y. Matsui, C. Shukunami, A. Takimoto, T. Goto, Y. Nishizaki, Y. Nakamichi, T. Kubo, T. Sano, S. Kato, Y. Hiraki, N. Yasui
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Local tenomodulin absence, angiogenesis, and MMP activation are associated with the rupture of the chordae tendineae cordis.2008
Author(s)
N. Kimura, C. Shukunami, D. Hakuno, M. Yoshioka, S. Miura, D. Docheva, T. Kimura, Y. Okada, G. Matsumura, T. Shin'oka, R. Yozu, J. Kobayashi, H. Ishibashi-Ueda, Y. Hiraki, K. Fukuda
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Journal Title
Circulation 118
Pages: 1737-1747
Related Report
Peer Reviewed
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[Journal Article] Cartilaginous features in matrix-producing carcinoma of the breast: four cases report with histochemical and immunohistochemical analysis of matrix molecules.2008
Author(s)
K. Kusafuka, K. Muramatsu, M. Kasami, K. Kuriki, K. Hirobe, I. Hayashi, H. Watanabe, Y. Hiraki, C. Shukunami, T. Mochizuki, T. Kameya
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Journal Title
Modern Pathology 21
Pages: 1282-1292
Related Report
Peer Reviewed
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[Journal Article] Dual effects of the membrane-anchored MMP regulator RECK on chondrogenic differentiation of ATDC5 cells.2007
Author(s)
S. Kondo, C. Shukunami, Y. Morioka, N. Matsumoto, R. Takahashi, J. Oh, T. Atsumi, A. Umezawa, A. Kudo, H. Kitayama, Y. Hiraki, M. Noda
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Journal Title
J. Cell Sci. 120
Pages: 849-857
Related Report
Peer Reviewed
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[Journal Article] Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis.2006
Author(s)
M. Yoshioka, S. Yuasa, K. Matsumura, T. Shiomi, C. Shukunami, Y. Okada, M. Mukai, H. Shin, R. Yozu, M. Sata, S. Ogawa, Y. Hiraki, K. Fukuda
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Journal Title
Nature Medicine 12
Pages: 1151-1159
NAID
Related Report
Peer Reviewed
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[Journal Article] Expression and localization of cartilage-specific matrix protein chondromodulin-I mRNA in salivary pleomorphic adenomas.2005
Author(s)
K. Kusafuka, K. Nakano, Y. Hiraki, C. Shukunami, H. Nagatsuka, N. Nagai, T. Takemura, Y. Sakaguchi, K. Okazaki, M. Kusafuka, H. Hisha, S. Ikehara
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Journal Title
Virchows Arch. 446
Pages: 34-40
Related Report
Peer Reviewed
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