Exploring the link between M1 macrophages and EMT of amniotic epithelial cells: implications for premature rupture of membranes
Abstract Background Despite increasing evidence supporting the role of an amniotic epithelial-mesenchymal transition (EMT) in the premature rupture of membranes (PROMs), it remains unclear if extracellular vesicle (EV) derived from M1 macrophages play a critical role in triggering the EMT of amnioti...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-03-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-025-03192-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850251708230270976 |
|---|---|
| author | Yuhua Gao Yanan Zhang Ningning Mi Wang Miao Jingmiao Zhang Yize Liu Zhikun Li Jiaxun Song Xiangchen Li Weijun Guan Chunyu Bai |
| author_facet | Yuhua Gao Yanan Zhang Ningning Mi Wang Miao Jingmiao Zhang Yize Liu Zhikun Li Jiaxun Song Xiangchen Li Weijun Guan Chunyu Bai |
| author_sort | Yuhua Gao |
| collection | DOAJ |
| description | Abstract Background Despite increasing evidence supporting the role of an amniotic epithelial-mesenchymal transition (EMT) in the premature rupture of membranes (PROMs), it remains unclear if extracellular vesicle (EV) derived from M1 macrophages play a critical role in triggering the EMT of amniotic epithelial cells (AECs). Results This study revealed that under inflammatory conditions, EV-miR-146a/155 from M1 macrophages could trigger EMTs and MMP-9 transcription in AECs, elevating the risk of PROM in both mice and humans. Introduction of EV-miR-155 led to inhibition of Ehf expression and reduced E-cadherin transcription in AECs. Meanwhile, EV-miR-146a activated the β-catenin/Tcf7 complex to promote the transcription of Snail, MMP-9, and miR-146a/155, inducing EMTs. Subsequently, EMT induction in AECs is associated with a loss of epithelial characteristics, disruption of cellular junctions, widening of intercellular spaces, and diminished biomechanical properties of the amniotic membrane. Conclusion Inflammatory stimulation prompts the polarization of macrophages in amniotic fluid into the M1 type, which subsequently secrete EVs laden with inflammatory miRNAs. These EVs trigger the EMT of AECs, causing the loss of their epithelial phenotype. Consequently, the biomechanical properties of the amnion deteriorate, ultimately leading to its rupture, posing risks relevant to pregnancy complications such as premature rupture of membranes. The results of this study provide insights into the pathogenesis of PROM and will aid in treatment development. |
| format | Article |
| id | doaj-art-0b757c14d22040bb938c1966d062f3f8 |
| institution | OA Journals |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-0b757c14d22040bb938c1966d062f3f82025-08-20T01:57:51ZengBMCJournal of Nanobiotechnology1477-31552025-03-0123112110.1186/s12951-025-03192-6Exploring the link between M1 macrophages and EMT of amniotic epithelial cells: implications for premature rupture of membranesYuhua Gao0Yanan Zhang1Ningning Mi2Wang Miao3Jingmiao Zhang4Yize Liu5Zhikun Li6Jiaxun Song7Xiangchen Li8Weijun Guan9Chunyu Bai10Precision Medicine Laboratory for Chronic Non-communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical UniversityDepartment of Obstetrics, Affiliated Hospital of Jining Medical UniversityCollege of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A&F UniversityPrecision Medicine Laboratory for Chronic Non-communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical UniversityPrecision Medicine Laboratory for Chronic Non-communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical UniversityPrecision Medicine Laboratory for Chronic Non-communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical UniversityPrecision Medicine Laboratory for Chronic Non-communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical UniversityPrecision Medicine Laboratory for Chronic Non-communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical UniversityCollege of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A&F UniversityInstitute of Animal Sciences, Chinese Academy of Agricultural SciencesPrecision Medicine Laboratory for Chronic Non-communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical UniversityAbstract Background Despite increasing evidence supporting the role of an amniotic epithelial-mesenchymal transition (EMT) in the premature rupture of membranes (PROMs), it remains unclear if extracellular vesicle (EV) derived from M1 macrophages play a critical role in triggering the EMT of amniotic epithelial cells (AECs). Results This study revealed that under inflammatory conditions, EV-miR-146a/155 from M1 macrophages could trigger EMTs and MMP-9 transcription in AECs, elevating the risk of PROM in both mice and humans. Introduction of EV-miR-155 led to inhibition of Ehf expression and reduced E-cadherin transcription in AECs. Meanwhile, EV-miR-146a activated the β-catenin/Tcf7 complex to promote the transcription of Snail, MMP-9, and miR-146a/155, inducing EMTs. Subsequently, EMT induction in AECs is associated with a loss of epithelial characteristics, disruption of cellular junctions, widening of intercellular spaces, and diminished biomechanical properties of the amniotic membrane. Conclusion Inflammatory stimulation prompts the polarization of macrophages in amniotic fluid into the M1 type, which subsequently secrete EVs laden with inflammatory miRNAs. These EVs trigger the EMT of AECs, causing the loss of their epithelial phenotype. Consequently, the biomechanical properties of the amnion deteriorate, ultimately leading to its rupture, posing risks relevant to pregnancy complications such as premature rupture of membranes. The results of this study provide insights into the pathogenesis of PROM and will aid in treatment development.https://doi.org/10.1186/s12951-025-03192-6Amniotic epithelial cellsExtracellular vesiclesMacrophagesEpithelial-mesenchymal transition |
| spellingShingle | Yuhua Gao Yanan Zhang Ningning Mi Wang Miao Jingmiao Zhang Yize Liu Zhikun Li Jiaxun Song Xiangchen Li Weijun Guan Chunyu Bai Exploring the link between M1 macrophages and EMT of amniotic epithelial cells: implications for premature rupture of membranes Journal of Nanobiotechnology Amniotic epithelial cells Extracellular vesicles Macrophages Epithelial-mesenchymal transition |
| title | Exploring the link between M1 macrophages and EMT of amniotic epithelial cells: implications for premature rupture of membranes |
| title_full | Exploring the link between M1 macrophages and EMT of amniotic epithelial cells: implications for premature rupture of membranes |
| title_fullStr | Exploring the link between M1 macrophages and EMT of amniotic epithelial cells: implications for premature rupture of membranes |
| title_full_unstemmed | Exploring the link between M1 macrophages and EMT of amniotic epithelial cells: implications for premature rupture of membranes |
| title_short | Exploring the link between M1 macrophages and EMT of amniotic epithelial cells: implications for premature rupture of membranes |
| title_sort | exploring the link between m1 macrophages and emt of amniotic epithelial cells implications for premature rupture of membranes |
| topic | Amniotic epithelial cells Extracellular vesicles Macrophages Epithelial-mesenchymal transition |
| url | https://doi.org/10.1186/s12951-025-03192-6 |
| work_keys_str_mv | AT yuhuagao exploringthelinkbetweenm1macrophagesandemtofamnioticepithelialcellsimplicationsforprematureruptureofmembranes AT yananzhang exploringthelinkbetweenm1macrophagesandemtofamnioticepithelialcellsimplicationsforprematureruptureofmembranes AT ningningmi exploringthelinkbetweenm1macrophagesandemtofamnioticepithelialcellsimplicationsforprematureruptureofmembranes AT wangmiao exploringthelinkbetweenm1macrophagesandemtofamnioticepithelialcellsimplicationsforprematureruptureofmembranes AT jingmiaozhang exploringthelinkbetweenm1macrophagesandemtofamnioticepithelialcellsimplicationsforprematureruptureofmembranes AT yizeliu exploringthelinkbetweenm1macrophagesandemtofamnioticepithelialcellsimplicationsforprematureruptureofmembranes AT zhikunli exploringthelinkbetweenm1macrophagesandemtofamnioticepithelialcellsimplicationsforprematureruptureofmembranes AT jiaxunsong exploringthelinkbetweenm1macrophagesandemtofamnioticepithelialcellsimplicationsforprematureruptureofmembranes AT xiangchenli exploringthelinkbetweenm1macrophagesandemtofamnioticepithelialcellsimplicationsforprematureruptureofmembranes AT weijunguan exploringthelinkbetweenm1macrophagesandemtofamnioticepithelialcellsimplicationsforprematureruptureofmembranes AT chunyubai exploringthelinkbetweenm1macrophagesandemtofamnioticepithelialcellsimplicationsforprematureruptureofmembranes |