Transcriptomics of tissue exosomes to investigate miR-195-5p’s amelioration of endometrial fibrosis via the YAP-Smad7 pathway: an animal study

A significant research gap exists regarding the role of tissue exosomes in intrauterine adhesions (IUAs). This study aims to investigate the involvement of miR-195-5p and its regulatory network in IUAs through the analysis of tissue exosomes. Exosomes from rat uterine tissue with intrauterine adhesions were analyzed via transcriptomics to identify downstream target genes of miR-195-5p, cross-referencing with the human endometrial transcriptomics database GSE224093. Dual luciferase labeling confirmed miRNA-target gene interactions. The therapeutic efficacy of a miR-195-5p agonist was assessed in vivo through HE staining, Masson staining, and mating tests. The mechanisms underlying extracellular matrix (ECM) deposition and myofibroblast transdifferentiation in endometrial fibrosis were investigated both in vitro and in vivo using RT-PCR, Western Blot, immunofluorescence, and immunohistochemistry. Migration ability of endometrial stromal cells was evaluated using CCK8, scratch tests, and Transwell assays. Finally, the clinical potential of miR-195-5p was compared with autologous adipose-derived mesenchymal stem cells. The expression of miR-195-5p in uterine tissue exosomes from intrauterine adhesions was found to be decreased. Treatment with a miR-195-5p agonist resulted in improved endometrial health, reduced fibrosis, increased glandular density, and enhanced birth rates in rats. Both in vivo and in vitro experiments confirmed that miR-195-5p decreased ECM deposition, reduced myofibroblast transdifferentiation, and inhibited the migration of endometrial stromal cells. This was achieved through the downregulation of YAP expression in the Hippo pathway and the upregulation of Smad7. Notably, the therapeutic efficacy of miR-195-5p agonists was comparable to that of stem cell therapy, offering promising avenues for clinical application. Differential expression of miR-195-5p in tissue exosomes can reduce ECM deposition and myofibroblast transdifferentiation, improving endometrial fibrosis by regulating the YAP-Smad7 pathway in the Hippo signaling cascade.