PMID- 37226011 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20231026 IS - 2629-3277 (Electronic) IS - 2629-3277 (Linking) VI - 19 IP - 6 DP - 2023 Aug TI - Exosomes from Human Umbilical Cord Mesenchymal Stem Cells Facilitates Injured Endometrial Restoring in Early Repair Period through miR-202-3p Mediating Formation of ECM. PG - 1954-1964 LID - 10.1007/s12015-023-10549-7 [doi] AB - Endometrial damage repair disorder is the main reason of intrauterine adhesions (IUA) and thin endometrium (TA), which is caused by curettage or infection. Exosomal miRNAs derived from human umbilical cord mesenchymal stem cells (hucMSCs) were reported to play an important role in damage repair disorder, including endometrial fibrosis. In this study, we aimed to investigate the role of hucMSCs-derived exosomal microRNA-202-3p (miR-202-3p) in endometrial damage repair. We established rat endometrial injury model according to curettage to mimic women curettage abortion operation. The miRNA array analysis indicated that miR-202-3p was increased and matrix metallopeptidase 11 (MMP11) was decreased in the exosomes-treated rat uterine tissues. Bioinformatics analysis suggested that MMP11 is the target gene of miR-202-3p. We observed that the mRNA and protein of MMP11 were significantly decreased in exosome treatment group on day 3, and the components of extracellular matrix (ECM) COL1A1, COL3A1, COLVI and fibronectin (FN) protein were increased. And we found that when the injured human stromal cells were treated with miR-202-3p overexpression exosomes, the COLVI and FN were also upregulated in protein and mRNA expression level. For the first time MMP11 was proved to be the target gene of miR-202-3p by dual luciferase reporter system. At last, we found the state of stromal cells was better in miR-202-3p overexpression exosomes group compared to exosomes group, and miR-202-3p overexpression exosomes markedly upregulated the FN and collagen on day 3 after endometrial injury. We thought that miR-202-3p overexpression exosomes promoted endometrial repair by regulating ECM remodeling in early repair of damaged endometrium. Taken together, these experimental findings may provide a theoretical basis for understanding endometrial repair and an insight into the clinical treatment for IUA. Human umbilical cord mesenchymal stem cells exosomal miR-202-3p could regulate the expression of MMP11 and promote the accumulation of extracellular matrix, such as COL1A1, COL3A1, COLVI, FN, in the early repair period of endometrial injury. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Wang, Shufang AU - Wang S AD - Department of Reproduction and Physiology, National Research Institute for Family Planning, Beijing, 100081, China. AD - National Research Institute for Family Planning, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100081 & 100730, China. AD - Department of Forensic Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan, China. FAU - Liu, Tingting AU - Liu T AUID- ORCID: 0000-0003-3451-3157 AD - Department of Reproduction and Physiology, National Research Institute for Family Planning, Beijing, 100081, China. AD - National Research Institute for Family Planning, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100081 & 100730, China. FAU - Nan, Nan AU - Nan N AD - Department of Reproduction and Physiology, National Research Institute for Family Planning, Beijing, 100081, China. AD - National Research Institute for Family Planning, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100081 & 100730, China. FAU - Lu, Cong AU - Lu C AD - Department of Reproduction and Physiology, National Research Institute for Family Planning, Beijing, 100081, China. AD - National Research Institute for Family Planning, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100081 & 100730, China. FAU - Liang, Min AU - Liang M AD - Department of Reproduction and Physiology, National Research Institute for Family Planning, Beijing, 100081, China. AD - National Research Institute for Family Planning, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100081 & 100730, China. FAU - Wang, Siyu AU - Wang S AD - Department of Reproduction and Physiology, National Research Institute for Family Planning, Beijing, 100081, China. AD - National Research Institute for Family Planning, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100081 & 100730, China. FAU - Wang, Hu AU - Wang H AD - National Research Institute for Family Planning, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100081 & 100730, China. FAU - He, Bin AU - He B AD - Department of Reproduction and Physiology, National Research Institute for Family Planning, Beijing, 100081, China. AD - National Research Institute for Family Planning, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100081 & 100730, China. FAU - Chen, Xihua AU - Chen X AD - Department of Reproduction and Physiology, National Research Institute for Family Planning, Beijing, 100081, China. xhchen.bio@outlook.com. AD - National Research Institute for Family Planning, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100081 & 100730, China. xhchen.bio@outlook.com. FAU - Xu, Xiangbo AU - Xu X AD - Department of Reproduction and Physiology, National Research Institute for Family Planning, Beijing, 100081, China. xuxiangbo@nrifp.org.cn. AD - National Research Institute for Family Planning, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100081 & 100730, China. xuxiangbo@nrifp.org.cn. FAU - Zheng, Yufeng AU - Zheng Y AD - School of Materials Science and Engineering, Peking University, Beijing, 100871, China. yfzheng@pku.edu.cn. AD - International Research Organization for Advanced Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-Ku, Kumamoto, 860-8555, Japan. yfzheng@pku.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230525 PL - United States TA - Stem Cell Rev Rep JT - Stem cell reviews and reports JID - 101752767 RN - EC 3.4.24.- (Matrix Metalloproteinase 11) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - 0 (MIRN202 microRNA, human) SB - IM MH - Humans MH - Female MH - Rats MH - Animals MH - *Exosomes/genetics/metabolism MH - Matrix Metalloproteinase 11/metabolism MH - *MicroRNAs/genetics/metabolism MH - Endometrium/metabolism MH - *Mesenchymal Stem Cells/metabolism MH - Extracellular Matrix/metabolism MH - Umbilical Cord/metabolism MH - RNA, Messenger/metabolism OTO - NOTNLM OT - Endometrium OT - Exosome OT - Extracellular matrix OT - Fibrosis OT - Intrauterine adhesions OT - miR-202-3p EDAT- 2023/05/25 01:07 MHDA- 2023/10/23 12:45 CRDT- 2023/05/24 23:32 PHST- 2023/04/27 00:00 [accepted] PHST- 2023/10/23 12:45 [medline] PHST- 2023/05/25 01:07 [pubmed] PHST- 2023/05/24 23:32 [entrez] AID - 10.1007/s12015-023-10549-7 [pii] AID - 10.1007/s12015-023-10549-7 [doi] PST - ppublish SO - Stem Cell Rev Rep. 2023 Aug;19(6):1954-1964. doi: 10.1007/s12015-023-10549-7. Epub 2023 May 25.