| Project/Area Number |
21890022
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
ITOH Fumiko University of Tsukuba, 大学院・人間総合科学研究科, 助教 (70502582)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥2,652,000 (Direct Cost: ¥2,040,000、Indirect Cost: ¥612,000)
Fiscal Year 2010: ¥1,261,000 (Direct Cost: ¥970,000、Indirect Cost: ¥291,000)
Fiscal Year 2009: ¥1,391,000 (Direct Cost: ¥1,070,000、Indirect Cost: ¥321,000)
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| Keywords | TGF-・ / 血管新生 / Smad2 / 3 / conditional knockout / リンパ管 / TGF-β / Smad2/3 / LYVE-1 / N-cadherin |
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| Research Abstract |
In order to elucidate molecular mechanisms by which TGF-β/ALK5/Smad2/3 pathway regulates vascular development, we established mouse embryonic endothelial cells (MEECs) from Smad2/3 conditionally inactivated mice. When we checked the reaction against for the shear stress, the Smad2/3KO MEECs did not respond it. Then we analyzed the molecular mechanisms with mRNA and miRNA arrays analysis and found that the expression of some cadherins were reduced in Smad2/3 KO MEEC compared to the wild type MEECs.
Although TGF-β signaling is known to play key roles in angiogenesis, it remains veiled how TGF-β regulates lymphangiogenesis. To elucidate molecular mechanisms by which TGF-β pathway controls lymphatic vascular development, we conditionally inactivated TGF-β type II receptor (TβRII) in LECs using Prox1-Cre-ER transgenic mice. When we administered Tamoxifen (TM) at E10.5 and E11.5, TβRIIF/F ; Prox1-CreER embryos showed edema at E14.5. Therefore we stained blood and lymphatic vessels with anti-PECAM-1 and anti-LYVE-1 antibodies, respectively. Interestingly, blood vessel seemed to be well-established, whereas lymphatic vessels merely existed though they were ragged and poorly organized. These data indicated that TGF-β signaling is indispensable for maintenance of lymphatic vessel integrities.
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