MSC-derived exosomes improve endometrial fibrosis via the lncRNA IGF2R/ miR-143-5p/AQP8 axis

Endometrial injury (EI) is frequently associated with intrauterine adhesions, endometrial thinning, amenorrhea, and infertility. In recent years, stem cells and their exosomes have been shown to have significant tissue repair efficacy. However, the role and probable mechanism of human umbilical cord mesenchymal stem cells (hUMSC-Exo) in endometrial healing remains unclear.

To build an EI model, in vivo investigations were carried out utilizing C57BL/6 mechanical manipulation. Hematoxylin-eosin staining and Masson Trichrome Staining were employed to examine morphological changes in the mouse uterus. TGF-β1 treatment was employed in an in vitro experiment to create an injury model for human endometrial stromal cells (hESCs). The expression of fibrosis-related molecules in uterine tissue and hESCs was investigated using Western blot and immunofluorescence labeling.

In animal experiments, after intervention with hUMSC-Exo, the fibrotic damage and expression of receptive molecules in the uterine tissue of EI mice were significantly repaired. Bioinformatics analysis predicts the high expression of lncRNA IGF2R in hUMSC-Exo and its relationship with fibrosis-related molecule aquaporin 8 (AQP8). In cell experiments, knocking down lncRNA IGF-2R in hUMSC-Exo or directly knocking down AQP8 in hESCs resulted in a significant increase in fibrosis-related molecule expression of hESCs.

In conclusion, our findings imply that hUMSC-Exo can prevent fibrosis via the AQP8/miR-143-5p/lncRNA IGF2R axis, hence reducing mechanically caused EI. Our findings offer fresh approaches and plans for using hUMSC-Exo to treat EI.