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Cell Res.:离子通道CFTR调节早期胚胎发育新进展

来源:生物谷 2012-06-11 10:46

6月5日,Cell Res.杂志在线报道了离子通道蛋白通过调节HCO3-跨膜运输,调节miR-125b进而调控胚胎发育的重要进展。尽管已知HCO3-是早期胚胎发育所必须的,其确切机制尚不明了。

囊性纤维化跨膜传导调节因子(CFTR)可作为HCO3-的跨膜通道。研究发现,在着床前胚胎发育过程中,通过CFTR介导的HCO3-涌入细胞,HCO3-可作为环境信息调节miR-125b的表达。实验结果显示,通过施加特异性CFTR抑制因子或敲除CFTR基因,能抑制HCO3-在着床前胚胎发育过程中的这一调节作用。而注射miR-125b前提可逆转这一效应。

在人类及小鼠胚胎中,下调miR-125b可上调p53信号通路级联反应。miR-125b的激活有赖于sAC/PKA依赖的NF-κB核转运。这些研究结果揭示,CFTR在联系着床前胚胎微环境中HCO3-与miR-125b活化的信号转导过程中发挥重要作用。这项研究还证实,离子通道在调节miRNA过程中可发挥重要作用。(生物谷bioon.com)

CFTR mediates bicarbonate-dependent activation of miR-125b in preimplantation embryo development

Yong Chao Lu1,2,3,6,*, Hui Chen1,2,*, Kin Lam Fok1,2,*, Lai Ling Tsang1,2, Mei Kuen Yu1,2, Xiao Hu Zhang1,2, Jing Chen1,2, Xiaohua Jiang1,2,4, Yiu Wa Chung1,2, Alvin Chun Hang Ma5, Anskar Yu Hung Leung5, He Feng Huang1,3 and Hsiao Chang Chan1,2,4,7

Although HCO3? is known to be required for early embryo development, its exact role remains elusive. Here we report that HCO3? acts as an environmental cue in regulating miR-125b expression through CFTR-mediated influx during preimplantation embryo development. The results show that the effect of HCO3? on preimplantation embryo development can be suppressed by interfering the function of a HCO3?-conducting channel, CFTR, by a specific inhibitor or gene knockout. Removal of extracellular HCO3? or inhibition of CFTR reduces miR-125b expression in 2 cell-stage mouse embryos. Knockdown of miR-125b mimics the effect of HCO3? removal and CFTR inhibition, while injection of miR-125b precursor reverses it. Downregulation of miR-125b upregulates p53 cascade in both human and mouse embryos. The activation of miR-125b is shown to be mediated by sAC/PKA-dependent nuclear shuttling of NF-κB. These results have revealed a critical role of CFTR in signal transduction linking the environmental HCO3? to activation of miR-125b during preimplantation embryo development and indicated the importance of ion channels in regulation of miRNAs.

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