Effects of miR-214-5p and miR-21-5p in hypoxic endometrial epithelial-cell-derived exosomes on human umbilical cord mesenchymal stem cells  

作　　者：Wan-Yu Zhang Han-Bi Wang Cheng-Yan Deng 

机构地区：[1]Department of Obstetrics and Gynecology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China [2]Department of Obstetrics and Gynecology,Peking Union Medical College Hospital,Beijing 100730,China

出　　处：《World Journal of Stem Cells》2024年第11期906-925,共20页世界干细胞杂志（英文）

基　　金：Supported by the National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-080 and No.2022-PUMCH-C-064.

摘　　要：BACKGROUND Thin endometrium seriously affects endometrial receptivity,resulting in a significant reduction in embryo implantation,and clinical pregnancy and live birth rates,and there is no gold standard for treatment.The main pathophysiological characteristics of thin endometrium are increased uterine arterial blood flow resistance,angiodysplasia,slow growth of the glandular epithelium,and low expression of vascular endothelial growth factor,resulting in endometrial epithelial cell(EEC)hypoxia and endometrial tissue aplasia.Human umbilical cord mesenchymal stem cells(HucMSCs)promote repair and regeneration of damaged endometrium by secreting microRNA(miRNA)-carrying exosomes.However,the initiation mechanism of HucMSCs to repair thin endometrium has not yet been clarified.AIM To determine the role of hypoxic-EEC-derived exosomes in function of HucMSCs and explore the potential mechanism.METHODS Exosomes were isolated from normal EECs(EEC-exs)and hypoxia-damaged EECs(EECD-exs),before characterization using Western blotting,nanoparticletracking analysis,and transmission electron microscopy.HucMSCs were cocultured with EEC-exs or EECD-exs and differentially expressed miRNAs were determined using sequencing.MiR-21-5p or miR-214-5p inhibitors or miR-21-3p or miR-214-5p mimics were transfected into HucMSCs and treated with a signal transducer and activator of transcription 3(STAT3)activator or STAT3 inhibitor.HucMSC migration was assessed by Transwell and wound healing assays.Differentiation of HucMSCs into EECs was assessed by detecting markers of stromal lineage(Vimentin and CD13)and epithelial cell lineage(CK19 and CD9)using Western blotting and immunofluorescence.The binding of the miRNAs to potential targets was validated by dual-luciferase reporter assay.RESULTS MiR-21-5p and miR-214-5p were lowly expressed in EECD-ex-pretreated HucMSCs.MiR-214-5p and miR-21-5p inhibitors facilitated the migratory and differentiative potentials of HucMSCs.MiR-21-5p and miR-214-5p targeted STAT3 and protein inhibitor of activated

关 键 词：Endometrial epithelial cells EXOSOMES Human umbilical cord mesenchymal stem cells MiR-214-5p/miR-21-5p Signal transducer and activator of transcription 3 

分 类 号：R745[医药卫生—神经病学与精神病学]