Suppression of Sproutys has a therapeutic effect for a mouse model of ischemia by enhancing angiogenesis.
Suppression of Sproutys has a therapeutic effect for a mouse model of ischemia by enhancing angiogenesis.
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DOI：
10.1371/journal.pone.0005467
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Yoshimura A
中科院分区：
文献类型：
--
作者：
Taniguchi K;Sasaki K;Watari K;Yasukawa H;Imaizumi T;Ayada T;Okamoto F;Ishizaki T;Kato R;Kohno R;Kimura H;Sato Y;Ono M;Yonemitsu Y;Yoshimura A
芽胞蛋白(Sprouty Proteins，Sproutys)抑制受体酪氨酸激酶信号转导，控制分支形态发生的各个方面。在这项研究中，我们利用基因打靶和短发夹状RNA(ShRNA)敲除策略，研究了Sproutys在血管生成中的生理功能。Sprouty2和Sprouty4双基因敲除(KO)(DKO)小鼠因心血管缺陷在E12.5左右胚胎致死。与野生型(WT)小鼠相比，Sprouty4KO小鼠的外周血管数量增加，但淋巴管数量没有增加。Sprout4 KO小鼠比WT小鼠对后肢缺血和软组织缺血的抵抗力更强，因为Sprout4缺乏会加速新生血管的形成。此外，通过靶向shRNA抑制Sprouty2和Sprouty4在体内的表达加速血管生成，并在小鼠后肢缺血模型中具有治疗作用。这些数据表明，Sproutys是体内血管生成的重要生理负性调节因子，是治疗外周缺血性疾病的新靶点。
Sprouty proteins (Sproutys) inhibit receptor tyrosine kinase signaling and control various aspects of branching morphogenesis. In this study, we examined the physiological function of Sproutys in angiogenesis, using gene targeting and short-hairpin RNA (shRNA) knockdown strategies. Sprouty2 and Sprouty4 double knockout (KO) (DKO) mice were embryonic-lethal around E12.5 due to cardiovascular defects. The number of peripheral blood vessels, but not that of lymphatic vessels, was increased in Sprouty4 KO mice compared with wild-type (WT) mice. Sprouty4 KO mice were more resistant to hind limb ischemia and soft tissue ischemia than WT mice were, because Sprouty4 deficiency causes accelerated neovascularization. Moreover, suppression of Sprouty2 and Sprouty4 expression in vivo by shRNA targeting accelerated angiogenesis and has a therapeutic effect in a mouse model of hind limb ischemia. These data suggest that Sproutys are physiologically important negative regulators of angiogenesis in vivo and novel therapeutic targets for treating peripheral ischemic diseases.
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DOI：
10.1016/j.jtcvs.2004.02.036
发表时间：
2004-10-01
影响因子：
6
作者：
Schalch, P;Patejunas, G;Rosengart, TK
通讯作者：
Rosengart, TK
DOI：
10.1073/pnas.0604144103
发表时间：
2006-09-26
影响因子：
11.1
作者：
Sasaki, Ken-ichiro;Heeschen, Christopher;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
影响因子：
21.3
作者：
Sasaki, A;Taketomi, T;Yoshimura, A
通讯作者：
Yoshimura, A
影响因子：
11.8
作者：
Fish, Jason E.;Santoro, Massimo M.;Morton, Sarah U.;Yu, Sangho;Yeh, Ru-Fang;Wythe, Joshua D.;Lvey, Kathryn N.;Bruneau, Benoit G.;Stainier, Didier Y. R.;Srivastava, Deepak
通讯作者：
Srivastava, Deepak
影响因子：
3.1
作者：
DAMATO, R;WESLOWSKI, E;SMITH, LEH
通讯作者：
SMITH, LEH