Elucidation of diversity and universality in angiogenesis by in vivo imaging
| Project/Area Number |
16H05125
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Research Collaborator |
Yuge Shinya
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 血管新生 / 創傷治癒 / 虚血 / 内皮細胞 / ペリサイト / 蛍光イメージング / ゼブラフィッシュ / 血管内皮細胞 / イメージング / 腫瘍血管新生 |
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| Outline of Final Research Achievements |
To investigate how endothelial cells (ECs) and pericytes (PCs) establish blood vessels during ischemia-induced angiogenesis, we developed a live-imaging system to analyze cutaneous angiogenesis in adult zebrafish. Cutaneous injury immediately induced angiogenesis. Tortuous and disorganized vessel networks formed within a few weeks after the injury and subsequently normalized through vessel regression in a few months. Upon injury, severed vessels elongated and anastomosed with each other. Thereafter, repaired vessels and adjacent uninjured vessels became tortuous by increasing the number of ECs. In parallel, PCs divided and migrated to cover the tortuous blood vessels. ECs sprouted from the PC-covered tortuous vessels, suggesting that EC sprouting does not require PC detachment from the vessel wall. Thus, live imaging of cutaneous angiogenesis in adult zebrafish enables us to clarify how ECs and PCs develop new blood vessels during cutaneous angiogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、創傷治癒に伴う血管新生において内皮細胞・ペリサイトが損傷部位に血管網を構築するプロセスの全貌を明らかにした。特に、血管新生におけるペリサイトの役割に関して、これまでの概念と矛盾する現象を捉え、血管新生におけるペリサイトの新たな役割を示した点で学術的な意義がある。また、癌や糖尿病網膜症では、病的な血管新生によってペリサイトの被覆が欠如した無秩序で機能的に未熟な血管が作られ病態を悪化させることから、病的血管新生が関わる疾患の病態解明、さらには治療法開発につながることが期待される。さらに、虚血性疾患などに対する効果的な血管再生療法の開発にも貢献できる。
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Report
(4 results)
Research Products
(50 results)
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[Journal Article] Rap1b promotes Notch signal-mediated hematopoietic stem cell development by enhancing integrin-mediated cell adhesion.2019
Author(s)
Rho S., Kobayashi I., Oguri-Nakamura E., Ando K., Fujiwara M., Kamimura N., Hirata H., Iida A., Iwai Y., Mochizuki N., Fukuhara S.
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Journal Title
Developmental Cell
Volume: 印刷中
Issue: 5
Pages: 1-16
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Lysophosphatidic acid receptor 4 activation augments drug delivery in tumors by tightening endothelial cell-cell contact.2017
Author(s)
Takara K., Eino D., Ando K., Yasuda D., Naito H., Tsukada Y., Iba T., Wakabayashi T., Muramatsu F., Kidoya H., Fukuhara S., Mochizuki N., Ishii S., Kishima H., Takakura N.
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Journal Title
Cell Reports
Volume: 20
Issue: 9
Pages: 2072-2086
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] CCM2 and PAK4 act downstream of atrial natriuretic peptide signaling to promote cell spreading.2017
Author(s)
Miura K, Nojiri T, Akitake Y, Ando K, Fukuhara S, Zenitani M, Kimura T, Hino J, Miyazato M, Hosoda H, Kangawa K.
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Journal Title
Biochem J.
Volume: 474
Issue: 11
Pages: 1897-1918
DOI
Related Report
Peer Reviewed
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[Journal Article] Flow-dependent endothelial YAP regulation that contributes to vessel maintenance.2017
Author(s)
Nakajima H, Yamamoto K, Agarwala S, Terai K, Fukui H, Fukuhara S, Ando K, Miyazali T, Yokota Y, Sxhmelzer E, Belting H, Affolter M, Lecaudey, Mochizuki N
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Journal Title
Developmental Cell
Volume: 40
Issue: 6
Pages: 523-536
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Osteocrin, a secretory peptide from heart, contributes to cranial osteogenesis in zebrafish2016
Author(s)
Chiba A, Watanabe-Takano H, Terai K, Fukui H, Miyazaki T, Uemura M, Hashimoto H, Hibi M, Fukuhara S, Mochizuki N
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Journal Title
Development
Volume: 144
Pages: 334-344
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Protein kinase A (PKA) Type I interacts with P-Rex1, a Rac guanine nucleotide exchange factor: Effect on PKA localization and P-Rex1 signaling.2016
Author(s)
Chávez-Vargas L., Adame-García S.R., Cervantes-Villagrana R.D., Castillo-Kauil A., Bruystens J.G.H., Fukuhara S., Taylor S.S., Mochizuki N., Reyes-Cruz G., Vázquez-Prado J.
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Journal Title
J. Biol. Chem.
Volume: 291
Issue: 12
Pages: 6182-6199
DOI
Related Report
Peer Reviewed
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