"miR-181d-5p, which is upregulated in fetal growth restriction placentas, inhibits trophoblast fusion via CREBRF"

作者全名："Wu, Zhi-Hong; Li, Fang-Fang; Ruan, Ling-Ling; Feng, Qian; Zhang, Shuang; Li, Zhuo-Hang; Otoo, Antonia; Tang, Jing; Fu, Li-Juan; Liu, Tai-Hang; Ding, Yu-Bin"

作者地址："[Wu, Zhi-Hong; Ding, Yu-Bin] Chongqing Med Univ, Dept Obstet & Gynecol, Women & Childrens Hosp, 120 Longshan Rd, Chongqing 401147, Peoples R China; [Wu, Zhi-Hong; Li, Fang-Fang; Ruan, Ling-Ling; Zhang, Shuang; Li, Zhuo-Hang; Otoo, Antonia; Tang, Jing; Liu, Tai-Hang; Ding, Yu-Bin] Minist Educ China & Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chongqing, Peoples R China; [Fu, Li-Juan] Chongqing Med Univ, Sch Tradit Chinese Med, Dept Pharmacol, Chongqing, Peoples R China; [Fu, Li-Juan] Changsha Med Univ, Acad Workstat, Changsha, Peoples R China; [Feng, Qian] Chongqing Med Univ, Chongqing Key Lab Tradit Chinese Med Prevent & Cu, Chongqing, Peoples R China"

通信作者："Ding, YB (通讯作者)，Chongqing Med Univ, Dept Obstet & Gynecol, Women & Childrens Hosp, 120 Longshan Rd, Chongqing 401147, Peoples R China.; Liu, TH; Ding, YB (通讯作者)，Minist Educ China & Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chongqing, Peoples R China.; Fu, LJ (通讯作者)，Chongqing Med Univ, Sch Tradit Chinese Med, Dept Pharmacol, Chongqing, Peoples R China."

来源：JOURNAL OF ASSISTED REPRODUCTION AND GENETICS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001167229300001

JCR分区：Q1

影响因子：3.2

年份：2023

卷号：40

期号：11

开始页：2725

结束页：2737

文献类型：Article

关键词：FGR; Placenta; Trophoblast cell; miR-181d-5p; CREBRF; Hypoxia

摘要："Purpose Fetal growth restriction (FGR) is a common complication characterized by impaired placental function and unfavorable pregnancy outcomes. This study aims to elucidate the expression pattern of miR-181d-5p in FGR placentas and explore its effects on trophoblast fusion. Methods The expression pattern of miR-181d-5p in human FGR placentas were evaluated using qRT-PCR. Western blot, qRT-PCR, and Immunofluorescence analysis were performed in a Forskolin (FSK)-induced BeWo cell fusion model following the transfection of miR-181d-5p mimic or inhibitor. Potential target genes for miR-181d-5p were identified by screening miRNA databases. The interaction between miR-181d-5p and Luman/CREB3 Recruitment Factor (CREBRF) was determined through a luciferase assay. Moreover, the effect of CREBRF on BeWo cell fusion was examined under hypoxic conditions. Results Aberrant up-regulation of miR-181d-5p and altered expression of trophoblast fusion makers, including glial cell missing 1 (GCM1), Syncytin1 (Syn1), and E-cadherin (ECAD), were found in human FGR placentas. A down-regulation of miR-181d-5p expression was observed in the FSK-induced BeWo cell fusion model. Transfection of the miR-181d-5p mimic resulted in the inhibition of BeWo cell fusion, characterized by a down-regulation of GCM1 and Syn1, accompanied by an up-regulation of ECAD. Conversely, the miR-181d-5p inhibitor promoted BeWo cell fusion. Furthermore, miR-181d-5p exhibited negative regulation of CREBRF, which was significantly down-regulated in the hypoxia-induced BeWo cell model. The overexpression of CREBRF was effectively ameliorated the impaired BeWo cell fusion induced by hypoxia. Conclusions Our study demonstrated that miR-181d-5p, which is elevated in FGR placenta, inhibited the BeWo cell fusion through negatively regulating the expression of CREBRF."

基金机构："National Natural Science Foundation of China [82171664, 81801458]; Natural Science foundation of Chongqing, China [CSTB2022NSCQ-LZX0062, cstc2021jcyj-msxmX0236]"

基金资助正文："This work was partly funded by the National Natural Science Foundation of China, (Grant no. 82171664, 81801458) and the Natural Science foundation of Chongqing, China, (Grant no. CSTB2022NSCQ-LZX0062, cstc2021jcyj-msxmX0236)."