TY - JOUR
T1 - Suppression of Sproutys has a therapeutic effect for a mouse model of ischemia by enhancing angiogenesis
AU - Taniguchi, Koji
AU - Sasaki, Ken Ichiro
AU - Watari, Kousuke
AU - Yasukawa, Hideo
AU - Imaizumi, Tsutomu
AU - Ayada, Toranoshin
AU - Okamoto, Fuyuki
AU - Ishizaki, Takuma
AU - Kato, Reiko
AU - Kohno, Ri Ichiro
AU - Kimura, Hiroshi
AU - Sato, Yasufumi
AU - Ono, Mayumi
AU - Yonemitsu, Yoshikazu
AU - Yoshimura, Akihiko
PY - 2009/5/8
Y1 - 2009/5/8
N2 - 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. Copyright:
AB - 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. Copyright:
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U2 - 10.1371/journal.pone.0005467
DO - 10.1371/journal.pone.0005467
M3 - Article
C2 - 19424491
AN - SCOPUS:65549111249
SN - 1932-6203
VL - 4
JO - PloS one
JF - PloS one
IS - 5
M1 - e5467
ER -