Abstract
Researchers have reported that miR-124-3p is highly expressed in patients with chronic endometritis. However, the underlying mechanism of miR-124-3p in the development of endometritis remains unclear. This study constructed an in vitro endometrial cell injury model by treating HEECs with 2 μg/mL LPS for 48 h. Then, 1 mg/kg LPS was injected into both sides of the mouse uterus to construct an in vivo endometrial injury model. The expression of miR-124-3p in human endometrial epithelial cells (HEECs) was assessed using RT‒qPCR. Exosomes were separated from bone marrow-derived mesenchymal stem cells (BMSCs) and cocultured with HEECs. A dual-luciferase reporter assay was performed to confirm the relationship between miR-124-3p and DUSP6. The results indicated that LPS inhibited HEEC viability in a time- and dose-dependent manner. The miR-124-3p inhibitor reversed the LPS-induced apoptosis and inhibition of HEEC viability. In addition, miR-124-3p could be transferred from BMSCs to HEECs by exosomes. Exosomes were derived from BMSCs treated with an NC inhibitor (BMSCs/NC Exo) or miR-124-3p inhibitor (BMSCs/anti-miR-124-3p Exo). In addition, BMSCs/anti-miR-124-3p Exo abolished the LPS-induced inhibition of HEEC viability and proliferation by inducing HEEC apoptosis. Moreover, BMSCs/anti-miR-124-3p Exo alleviated the LPS-induced inflammation of HEECs by upregulating DUSP6 and downregulating p-p65 and p-ERK. Furthermore, in an LPS-induced in vivo endometrial injury model, BMSCs/anti-miR-124-3p Exo increased the expression level of DUSP6 and decreased the expression levels of p-p65 and p-ERK. BMSCs/anti-miR-124-3p Exo protected against LPS-induced endometrial damage in vitro and in vivo by upregulating DUSP6 and downregulating p-p65 and p-ERK1/2. This study showed that BMSCs/anti-miR-124-3p Exo might be a potential alternative for the treatment of endometritis.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Funding
This study was supported by the Natural Science Foundation of Fujian Province (No. 2020J01986, and 2021J01236) and Fujian Provincial Finance Project (NO: BPB-CYH2021).
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Conceived and designed the study: Yihong Chen, Shan Zheng, and Juanbing Wei.
Performed the literature search and data extraction: Xiumei Zhao, Yi Zhang, and Suchai Yu.
Analysed the data: Xiumei Zhao and Yi Zhang. Drafted the manuscript: Yihong Chen, and Juanbing Wei.
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This study was reviewed and approved by the Ethics Committee of Fujian Medical University (ethics number: 2023-Y-0524). No patients were involved in this study.
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Chen, Y., Zheng, S., Zhao, X. et al. Unveiling the protective effects of BMSCs/anti-miR-124-3p exosomes on LPS-induced endometrial injury. Funct Integr Genomics 24, 32 (2024). https://doi.org/10.1007/s10142-024-01303-4
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DOI: https://doi.org/10.1007/s10142-024-01303-4