Unveiling the protective effects of BMSCs/anti-miR-124-3p exosomes on LPS-induced endometrial injury

• Published in: Functional & integrative genomics Vol. 24; no. 2; p. 32
• Main Authors: Chen, Yihong, Zheng, Shan, Zhao, Xiumei, Zhang, Yi, Yu, Suchai, Wei, Juanbing
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-04-2024; Springer Nature B.V
• Subjects: Animal Genetics and Genomics; Apoptosis; Biochemistry; Bioinformatics; Biomedical and Life Sciences; Bone marrow; Cell Biology; Cell growth; Cell injury; Endometritis; Endometrium; Epithelial cells; Exosomes; Extracellular signal-regulated kinase; Inflammation; Life Sciences; Lipopolysaccharides; Mesenchymal stem cells; Microbial Genetics and Genomics; MicroRNAs; Original Article; Plant Genetics and Genomics; Stem cells; Viability; Human endometrial epithelial cells; miR-124-3p; Exosomes; Endometritis; Mesenchymal stem cells
• ISSN: 1438-793X; 1438-7948
• DOI: 10.1007/s10142-024-01303-4

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.