Lysophosphatidic acid regulates murine blastocyst development by transactivation of receptors for heparin-binding EGF-like growth factor
Lysophosphatidic acid regulates murine blastocyst development by transactivation of receptors for heparin-binding EGF-like growth factor
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DOI：
10.1016/j.yexcr.2004.02.006
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发表时间：
2004-06-10
影响因子：
3.7
通讯作者：
Armant, DR
中科院分区：
文献类型：
--
作者：
Liu, ZT;Armant, DR
细胞内钙（Ca-i(2+)）通过各种途径的短暂升高加速了小鼠着床前发育和滋养细胞分化。几种g蛋白偶联受体（gpcr），包括溶血磷脂酸（LPA）受体（LPAR），通过动员EGF家族成员，包括肝素结合EGF样生长因子（HB-EGF），诱导Ca-i（2+）瞬态并反激活EGF受体（ErbB1）。由于HB-EGF在体外加速囊胚分化，我们研究了LPA和HB-EGF之间的串扰是否调节着床周发育。在小鼠囊胚分化过程中，胚胎快速组成表达LPAR、mRNA Signaling、LPA，仅在囊胚后期表达LPAR(2)，不表达LPAR(3)。与基于Ca-i（2+）的机制一致，Ca-i（2+）加速了滋养细胞的生长速度，这是囊胚分化的指标，Ca-i（2+）与BAPTA-ANI的螯合阻断了LPA的刺激。通过ErbB1或ErbB4干扰HB-EGF信号也可减弱LPA刺激。我们证实小鼠囊胚确实表达HB-EGF，并且LPA诱导HB-EGF在胚胎表面的短暂积累，这一积累被BAPTA-AM或蛋白质运输抑制剂brefeldin a阻断。我们得出结论，LPA加速囊胚瞬态和HB-EGF自分泌信号传导。HB-EGF分化通过其诱导Ca-i（2+）的能力激活ErbB I或ErbB4，这代表了滋养细胞中通过调动Ca-i（2+）的刺激进入的趋同信号通路。(C) 2004爱思唯尔公司版权所有。
Transient elevation of intracellular calcium (Ca-i(2+)) by various means accelerates murine preimplantation development and trophoblast differentiation. Several G-protein-coupled receptors (GPCRs), including the lysophosphatidic acid (LPA) receptor (LPAR), induce Ca-i(2+) transients and transactivate the EGF receptor (ErbB1) through mobilization of EGF family members, including heparin-binding EGF-like growth factor (HB-EGF). Because HB-EGF accelerates blastocyst differentiation in vitro, we examined whether crosstalk between LPA and HB-EGF regulates peri-implantation development. During mouse blastocyst differentiation, embryos expressed LPAR, mRNA Signaling, LPA rapidly constitutively, LPAR(2) only in late stage blastocysts and no LPAR(3). Consistent with a mechanism based on Ca-i(2+) accelerated the rate of trophoblast outgrowth, an index of blastocyst differentiation, and chelation of Ca-i(2+) with BAPTA-ANI blocked LPA stimulation. Interfering with HB-EGF signaling through ErbB1 or ErbB4 also attenuated LPA stimulation. We established that mouse blastocysts indeed express HB-EGF and that LPA induces the transient accumulation of HB-EGF on the embryo surface, which was blocked by treatment with either BAPTA-AM or the protein trafficking inhibitor, brefeldin A. We conclude that LPA accelerates blastocyst transients and HB-EGF autocrine signaling. Transactivation of ErbB I or ErbB4 by HB-EGF differentiation through its ability to induce Ca-i(2+) represent a convergent signaling pathway accessed in the trophoblast by stimuli that mobilize Ca-i(2+). (C) 2004 Elsevier Inc. All rights reserved.