Elabela-apelin receptor signaling pathway is functional in mammalian systems.
Elabela-apelin receptor signaling pathway is functional in mammalian systems.
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DOI：
10.1038/srep08170
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发表时间：
2015-02-02
影响因子：
4.6
通讯作者：
Gong DW
中科院分区：
文献类型：
--
作者：
Wang Z;Yu D;Wang M;Wang Q;Kouznetsova J;Yang R;Qian K;Wu W;Shuldiner A;Sztalryd C;Zou M;Zheng W;Gong DW
Elabela（ELA）或Toddler是最近发现的一种激素，其通过激活斑马鱼的G蛋白偶联受体（GPCR）apelin受体（APJ）而为心脏和血管的正常发育所需。本研究探讨ELA-APJ信号通路是否在哺乳动物系统中起作用。利用逆转录PCR，我们发现ELA是限制性表达在人类多能干细胞和成人肾脏，而APJ是更广泛的表达。我们接下来研究了重组哺乳动物细胞系统中的ELA-APJ信号通路。将ELA添加到过表达GFP-AJP融合蛋白的HEK 293细胞中导致融合受体的快速内化。在过表达人APJ的中国仓鼠卵巢（CHO）细胞中，ELA抑制cAMP产生（EC 50为11.1 nM），刺激ERK 1/2磷酸化（EC 50为14.3 nM），并弱诱导细胞内钙动员。 最后，我们测试了ELA在人脐血管内皮细胞中的生物学功能，并表明ELA通过与apelin不同的机制以剂量依赖性方式诱导血管生成并舒张小鼠主动脉血管。总的来说，我们证明了ELA-AJP信号通路在哺乳动物系统中是功能性的，表明ELA可能作为一种激素调节成年期和胚胎发育中的循环系统。
Elabela (ELA) or Toddler is a recently discovered hormone which is required for normal development of heart and vasculature through activation of apelin receptor (APJ), a G protein-coupled receptor (GPCR), in zebrafish. The present study explores whether the ELA-APJ signaling pathway is functional in the mammalian system. Using reverse-transcription PCR, we found that ELA is restrictedly expressed in human pluripotent stem cells and adult kidney whereas APJ is more widely expressed. We next studied ELA-APJ signaling pathway in reconstituted mammalian cell systems. Addition of ELA to HEK293 cells over-expressing GFP-AJP fusion protein resulted in rapid internalization of the fusion receptor. In Chinese hamster ovarian (CHO) cells over-expressing human APJ, ELA suppresses cAMP production with EC50 of 11.1 nM, stimulates ERK1/2 phosphorylation with EC50 of 14.3 nM and weakly induces intracellular calcium mobilization. Finally, we tested ELA biological function in human umbilical vascular endothelial cells and showed that ELA induces angiogenesis and relaxes mouse aortic blood vessel in a dose-dependent manner through a mechanism different from apelin. Collectively, we demonstrate that the ELA-AJP signaling pathways are functional in mammalian systems, indicating that ELA likely serves as a hormone regulating the circulation system in adulthood as well as in embryonic development.
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影响因子：
8.8
作者：
Rumjahn, S M;Javed, M A;Wong, N;Law, W E;Buxton, I L O
通讯作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Penninger, Josef M.