Overexpression of autotaxin, a lysophosphatidic acid-producing enzyme, enhances cardia bifida induced by hypo-sphingosine-1-phosphate signaling in zebrafish embryo
Overexpression of autotaxin, a lysophosphatidic acid-producing enzyme, enhances cardia bifida induced by hypo-sphingosine-1-phosphate signaling in zebrafish embryo
复制标题
斑马鱼胚胎中自分泌运动因子（一种溶血磷脂酸产生酶）的过度表达可增强由次鞘氨醇-1-磷酸信号传导诱导的贲门裂
DOI：
10.1093/jb/mvt114
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Aoki J
中科院分区：
文献类型：
--
作者：
Nakanaga K;Hama K;Kano K;Sato T;Yukiura H;Inoue A;Saigusa D;Tokuyama H;Tomioka Y;Nishina H;Kawahara A;Aoki J
溶血磷脂酸（LPA）和鞘氨醇-1-磷酸（S1P）是第二代溶血磷脂介质，它们通过自身同源受体发挥多种生物学功能。它们都存在于血流中，激活具有相似结构的受体（内皮分化基因受体），在脉管系统中具有相似的作用并具有血管活性。然而，目前尚不清楚这些溶血磷脂介质是否在每个受体的下游相互作用。在这里，我们提供了LPA信号抵消S1P信号的活体证据。通过注射产生lpa的酶Atx mrna在斑马鱼胚胎中过表达，胚胎表现为贲门裂，这是一种由S1P信号下调引起的表型。当引入无催化活性的Atx时，没有诱导类似的心脏表型。与atxmrna一起引入抗S1P受体（s1pr2/mil）或S1P转运体（spns2）的反义morpholino olignucleotides （MO）可协同增强心脏表型。当胚胎用anlpar1受体拮抗剂Ki16425或抗lpar1的MO处理时，atx诱导的心裂明显受到抑制。这些结果为LPA和S1P信号之间的串扰提供了第一个活体证据。
Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are second-generation lysophospholipid mediators that exert multiple biological functions through their own cognate receptors. They are both present in the blood stream, activate receptors with similar structures (endothelial differentiation gene receptors), have similar roles in the vasculature and are vasoactive. However, it is unclear whether these lysophospholipid mediators cross-talk downstream of each receptor. Here, we providein vivoevidence that LPA signaling counteracted S1P signaling. When autotaxin (Atx), an LPA-producing enzyme, was overexpressed in zebrafish embryos by injectingatxmRNA, the embryos showed cardia bifida, a phenotype induced by down-regulation of S1P signaling. A similar cardiac phenotype was not induced when catalytically inactive Atx was introduced. The cardiac phenotype was synergistically enhanced when antisense morpholino oligonucleotides (MO) against S1P receptor (s1pr2/mil) or S1P transporter (spns2) was introduced together withatxmRNA. The Atx-induced cardia bifida was prominently suppressed when embryos were treated with anlpar1receptor antagonist, Ki16425, or with MO againstlpar1. These results provide the firstin vivoevidence of cross-talk between LPA and S1P signaling.