Umbilical cord mesenchymal stem cell- derived exosomes reverse endometrial fibrosis by the miR-145-5p/ZEB2 axis in intrauterine adhesions

Research question: What is the specific mechanism of umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-exos) in regulating endometrial repair and regeneration?Design: In this study, UCMSC-exos were harvested by differential ultracentrifugation from umbilical cord mesenchymal stem cell culture supernatant and identified with western blotting, transmission electron microscopy and nanoparticle tracking analysis. Transforming growth factor-I31 (TGFI31) at different concentrations was used to construct the intrauterine adhesions cell model. The fibrotic markers were assessed by quantitative reverse transcription-polymerase chain reaction and western blotting. The effects of miR-145-5p over-expression on endometrial fibrosis were assessed. Dual luciferase assay was performed to verify the relationship between miR-145-5p and zinc finger E-box binding homeobox 2 (ZEB2).Results: The isolated UCMSC-exos had a typical cup-shaped morphology, expressed the specific exosomal markers Alix, CD63 and TSG101, and were approximately 50-150 nm in diameter. TGFI31 at 10 ng/ml significantly promoted endometrial fibrosis, which was reversed by 20 mu g/ml UCMSC-exos. Exosomal miR-145-5p ameliorated TGFI31-induced endometrial fibrosis. ZEB2 was inversely regulated by exosomal miR-145-5p as a direct target. Conclusions: UCMSC-exos might reverse endometrial stromal cell fibrosis by regulating the miR-145-5p/ZEB2 axis, representing a potential novel strategy to promote endometrial repair.