2010 Fiscal Year Final Research Report
The role of TGF-・・signaling in Angiogenesis
| 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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| Keywords | TGF-・ / 血管新生 / Smad2 / 3 / conditional knockout / リンパ管 |
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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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Research Products
(12 results)
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[Journal Article] TMEPAI, a transmembrane TGF-(3-inducible protein, sequesters Smad proteins from active participation in TGF-(3 signaling.2010
Author(s)
Watanabe Y, Itch S, Goto T, Ohnishi E, Inamitsu M, Itoh F, Satoh K, Wiercinska E, Yang W, Shi L, Tanaka A, Nakano N, Mommaas AM, Shibuya H, ten Duke P, Kato M.
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Journal Title
Mol.Cell 37
Pages: 123-134
Peer Reviewed
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[Journal Article] Poor vessel formation in Embryos from Knock-in Mice Expressing ALK5 with L45 loop mutation defective in Smad activation.2009
Author(s)
Itoh F, Itoh S, Carvalho R.L.C, Adachi T, Ema M, Goumans MJ, Larsson J, Takahashi S, Mummery CL, ten Duke P, Kato M.
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Journal Title
Lab.Invest. 89
Pages: 800-810
Peer Reviewed
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