Nr2e1基因下调参与了过量视黄酸诱导的小鼠脑部发育异常。

Nr2e1 Downregulation Is Involved in Excess Retinoic Acid-induced Developmental Abnormality in the Mouse Brain.

作者信息

Yu Juan, Guo Qian, Mu Jian Bing, Zhang Ting, Li Ren Ke, Xie Jun

机构信息

Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, Shanxi, China.

Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA.

出版信息

Biomed Environ Sci. 2017 Mar;30(3):185-193. doi: 10.3967/bes2017.026.

DOI:10.3967/bes2017.026

PMID:28427488

Abstract

OBJECTIVE

This study aimed to investigate the expression pattern and function of Nuclear receptor subfamily 2 group E member 1 (Nr2e1) in retinoic acid (RA)-induced brain abnormality.

METHODS

The mouse model of brain abnormality was established by administering 28 mg/kg RA, and neural stem cells (NSCs) were isolated from the mouse embryo and cultured in vitro. Nr2e1 expression was detected by whole mount in situ hybridization, RT-PCR, and Western blotting. Nr2e1 function was determined by transducing Nr2e1 shRNA into NSCs, and the effect on the sonic hedgehog (Shh) signaling pathway was assessed in the cells. In addition, the regulation of Nr2e1 expression by RA was also determined in vitro.

RESULTS

Nr2e1 expression was significantly downregulated in the brain and NSCs of RA-treated mouse embryos, and knockdown of Nr2e1 affected the proliferation of NSCs in vitro. In addition, a similar expression pattern of Nr2e1 and RA receptor (RAR) α was observed after treatment of NSCs with different concentrations of RA.

CONCLUSION

Our study demonstrated that Nr2e1 could be regulated by RA, which would aid a better understanding of the mechanism underlying RA-induced brain abnormality.

摘要

目的

本研究旨在探讨核受体亚家族2组E成员1（Nr2e1）在视黄酸（RA）诱导的脑异常中的表达模式及功能。

方法

通过给予28 mg/kg RA建立脑异常小鼠模型，从小鼠胚胎中分离神经干细胞（NSCs）并进行体外培养。采用全胚胎原位杂交、逆转录-聚合酶链反应（RT-PCR）及蛋白质免疫印迹法检测Nr2e1的表达。将Nr2e1短发夹RNA（shRNA）转导至NSCs中以确定Nr2e1的功能，并评估其对细胞中 Sonic Hedgehog（Shh）信号通路的影响。此外，还在体外确定了RA对Nr2e1表达的调节作用。