Down-regulation of Exosomal miR-214-3p Targeting CCN2 Contributes to Endometriosis Fibrosis and the Role of Exosomes in the Horizontal Transfer of miR-214-3p

Endometriosis (EMs) is defined as the presence of tissue which somewhat resembles endometrial glands and stroma outside the uterus, and elicits fibrosis. Fibrosis is the main factor resulting in pain and infertility, while the aetiology of endometrial fibrosis is unknown. There is strong evidence from numerous experiments showing that connective tissue growth factor (CCN2) plays a central role in fibrogenesis. Exosomal miR-214-3p can regulate the expression of CCN2 through binding to complementary sites in the 3' untranslated region. This study aimed to explore the role of exosomal miR-214-3p in endometriosis fibrosis and the relationship between CCN2 and miR-214-3p in endometriosis fibrosis. Our results demonstrated that miR-214-3p was significantly down-regulated and CCN2 was up-regulated in EMs ectopic lesion and stromal cells compared with EMs eutopic and endometrium of patients without endometriosis. Exosomal miR-214-3p can inhibit fibrosis in EMs through targeting CCN2. The results were explored and verified in vitro and in vivo, respectively. Cell co-culture was used to explore the contributions of exosomes to intercellular information transmission of miR-214-3p. The results showed that exosomes play a pivotal role in the transportation of miR-214-3p between cells. Furthermore, level of exosomal miR-214-3p in endometriosis patients' serum was lower than that in patients without endometriosis. In conclusion, exosomal miR-214-3p can inhibit fibrosis in EMs by targeting CCN2. MiR-214-3p may be considered as a bio-marker and has a potential therapeutic effect in EMs.