Evidence map›Paper›PMID 40770601›Full record

ArticleReproductive sciences (Thousand Oaks, Calif.)2025

Endometrial Mesenchymal Stem Cell-Derived Exosomal miR-4669 Promotes EMT in Adenomyosis by Inducing M2 Macrophage Polarization via the DUSP6/ERK Pathway.

Yingying Qiu, Xinjun Wei, Jian Cao, Jindan Wang, Qianru Dou, Fangfang Zhou, Xi Chen, Yongli Liu, Guiping Wan, Meihua Huang and 2 more

Abstract read
PubMed Publisher
In one paragraph

Article in Reproductive sciences (Thousand Oaks, Calif.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Transcriptomic and functional analysis of fibroid extracellular vesicles.Clinical science (London, England : 1979) · 2026
    Article
  6. CD11dGenes and immunity · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Yingying Qiu *Department of Obstetrics and Gynecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China.
Xinjun Wei *Department of Obstetrics and Gynecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China.
Jian Cao *Department of Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, 210004, China.
Jindan WangDepartment of Obstetrics and Gynecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China.
Qianru DouDepartment of Gynecology, The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, 221112, China.
Fangfang ZhouDepartment of Obstetrics and Gynecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China.
Xi ChenDepartment of Obstetrics and Gynecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China.
Yongli LiuDepartment of Gynecology, The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, 221112, China.
Guiping WanDepartment of Obstetrics and Gynecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China.
Meihua HuangDepartment of Obstetrics and Gynecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China.
Zhenli LiDepartment of Obstetrics and Gynecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China.
Tao GuiDepartment of Obstetrics and Gynecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China. guitaoemail@163.com.ORCID 0000-0003-4764-4834

Funding

Development Fund Project of the Affiliated Hospital of Xuzhou Medical University XYFY202322National Natural Science Foundation of China 81403321Science and Technology Project of Jiangsu Provincial Administration of Traditional Chinese Medicine MS2023039Science and Technology Project of Jiangsu Provincial Administration of Traditional Chinese Medicine MS2023079Science and Technology Project of Jiangsu Provincial Administration of Traditional Chinese Medicine ZD202419
6 · The paper itself

Abstract

Adenomyosis (AM), a gynecological disorder that severely affects female reproductive health. AM-associated macrophage (AAM) polarization-induced epithelial-mesenchymal transition (EMT) is a key driver of AM progression. In this study, we investigated the role and underlying mechanisms of endometrial mesenchymal stem cell (eMSC)-derived exosomes in regulating AAM polarization and the subsequent EMT of endometrial epithelial cells (EECs). In vitro coculture studies revealed that AM eutopic eMSCs markedly induced M2 macrophage polarization via exosomes and promoted EMT of EECs. Differentially expressed microRNAs (DE-miRNAs) between exosomes derived from normal eMSCs (N-eMSCs) and AM eutopic eMSCs (A-eMSCs) were identified using miRNA sequencing and miR-4669 was found to be the most significantly upregulated miRNA. Internalization of exosomal miR-4669 by macrophages induced their polarization toward the M2 phenotype and promoted the EMT of EECs. Mechanistic analysis using luciferase assay, mRNA sequencing, and rescue experiments revealed that miR-4669 induced M2 macrophage polarization via downregulation of DUSP6 and activation of MAPK/ERK signaling. The polarized M2 macrophages promoted the EMT of ISK cells via TGF-β1 secretion. In an AM xenograft mouse model, miR-4669 depletion inhibited AM progression by targeting the DUSP6/ERK1/2 pathway in macrophages. Overall, AM A-eMSC-derived exosomal miR-4669 facilitates M2 macrophage polarization by targeting the DUSP6/ERK signaling pathway, thereby promoting EMT of EECs via TGF-β1 secretion. These findings open avenues for developing novel preventive and therapeutic strategies for AM.

Indexed as

AdenomyosisDual Specificity Phosphatase 6EndometriumEpithelial-Mesenchymal TransitionExosomesMacrophagesMAP Kinase Signaling SystemMesenchymal Stem CellsMicroRNAsAnimalsFemaleHumansMiceDual Specificity Phosphatase 6DUSP6 protein, humanMicroRNAsAdenomyosisDUSP6EMTExosomesMacrophageMiR-4669

Identifiers

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.