Exosomes derived from BMSCs with miR-124-3p inhibitor protects against LPS-induced endometritis through regulation of DUSP6, p-p65 and p-ERK

Abstract

Endometritis seriously affects womens normal life and work. It has been found that microRNA-123-3p (miR-124-3p) expression is abnormally high expression in the patients of chronic endometritis. However, the underlying mechanism for miR-124-3p regulation of endometritis development remains unclear. In our study, we treated human endometrial epithelial cells (HEECs) with LPS to simulate endometrial injury in vitro. Then, HEEC was treated with miR-124-3p mimics and miR-124-3p inhibitor. Next, exosomes were separated from bone marrow-derived mesenchymal stem cells (BMSCs). In addition, BMSCs were co-cultured with HEEC. Later on, dual-luciferase reporter assay was carried out to validate the regulation between miR-124-3p and DUSP6. Results indicated that LPS inhibited the viability of HEEC in time and dose dependent manner. MiR-124-3p inhibitor reversed apoptosis and viability inhibition of HEEC which were induced by LPS. In addition, we also found exosomes could transfer miR-124-3p from BMSCs to HEEC. Besides, BMSCs/anti-miR-124-3p Exo was observed to abolish LPS-induced viability and proliferation inhibition of HEEC by inducing the apoptosis of HEEC. Moreover, BMSCs/anti-miR-124-3p Exo alleviated inflammation of HEEC induced by LPS via upregulating DUSP6 and downregulating p-p65 and p-ERK. Furthermore, BMSCs/anti-miR-124-3p Exo protected against LPS-induced endometritis in vivo by upregulating DUSP6 and downregulating p-p65 and p-ERK. In conclusion, we found that BMSCs/anti-miR-124-3p Exo might be a promising new alternative to treat endometritis.