自分泌运动因子过表达导致胚胎致死和血管缺陷。
Autotaxin overexpression causes embryonic lethality and vascular defects.
作者信息
Yukiura Hiroshi, Kano Kuniyuki, Kise Ryoji, Inoue Asuka, Aoki Junken
机构信息
Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan.
Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan; PREST, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan.
出版信息
PLoS One. 2015 May 19;10(5):e0126734. doi: 10.1371/journal.pone.0126734. eCollection 2015.
Autotaxin (ATX) is a secretory protein, which converts lysophospholipids to lysophosphatidic acid (LPA), and is essential for embryonic vascular formation. ATX is abundantly detected in various biological fluids and its level is elevated in some pathophysiological conditions. However, the roles of elevated ATX levels remain to be elucidated. In this study, we generated conditional transgenic (Tg) mice overexpressing ATX and examined the effects of excess LPA signalling. We found that ATX overexpression in the embryonic period caused severe vascular defects and was lethal around E9.5. ATX was conditionally overexpressed in the neonatal period using the Cre/loxP system, which resulted in a marked increase in the plasma LPA level. This resulted in retinal vascular defects including abnormal vascular plexus and increased vascular regression. Our findings indicate that the ATX level must be carefully regulated to ensure coordinated vascular formation.
自分泌运动因子（ATX）是一种分泌蛋白，可将溶血磷脂转化为溶血磷脂酸（LPA），对胚胎血管形成至关重要。在各种生物体液中均可大量检测到ATX，且在某些病理生理条件下其水平会升高。然而，ATX水平升高的作用仍有待阐明。在本研究中，我们构建了过表达ATX的条件转基因（Tg）小鼠，并研究了过量LPA信号的影响。我们发现胚胎期ATX过表达会导致严重的血管缺陷，并在E9.5左右致死。利用Cre/loxP系统在新生期条件性过表达ATX，导致血浆LPA水平显著升高。这导致视网膜血管缺陷，包括异常血管丛和血管消退增加。我们的研究结果表明，必须仔细调节ATX水平以确保血管形成的协调。
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