Transcriptomics of tissue exosomes to investigate miR-195-5p’s amelioration of endometrial fibrosis via the YAP-Smad7 pathway: an animal study
Abstract Background 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. Methods Exosomes from rat uterine tis...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-11-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-05871-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846158231959764992 |
|---|---|
| author | Jia-ming Chen Qiao-yi Huang Wei-hong Chen Jin-xiang Wu Ling-tao Zheng Hui-jie You Yan-chuan Shi Shu Lin Qi-rong Shi |
| author_facet | Jia-ming Chen Qiao-yi Huang Wei-hong Chen Jin-xiang Wu Ling-tao Zheng Hui-jie You Yan-chuan Shi Shu Lin Qi-rong Shi |
| author_sort | Jia-ming Chen |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| format | Article |
| id | doaj-art-38c114061cb645338c80aed30f4433ad |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-38c114061cb645338c80aed30f4433ad2024-11-24T12:41:21ZengBMCJournal of Translational Medicine1479-58762024-11-0122112110.1186/s12967-024-05871-8Transcriptomics of tissue exosomes to investigate miR-195-5p’s amelioration of endometrial fibrosis via the YAP-Smad7 pathway: an animal studyJia-ming Chen0Qiao-yi Huang1Wei-hong Chen2Jin-xiang Wu3Ling-tao Zheng4Hui-jie You5Yan-chuan Shi6Shu Lin7Qi-rong Shi8Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical UniversityDepartment of Gynaecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical UniversityDepartment of Gynaecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical UniversityDepartment of Reproductive Medicine, The Second Affiliated Hospital of Fujian Medical UniversityDepartment of Gynaecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical UniversityDepartment of Gynaecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical UniversityGroup of Neuroendocrinology, Garvan Institute of Medical ResearchGroup of Neuroendocrinology, Garvan Institute of Medical ResearchDepartment of Gynaecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical UniversityAbstract Background 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. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s12967-024-05871-8Tissue exosomesmiR-195-5pIntrauterine adhesionMyofibroblast transdifferentiationYAP–Smad7Hippo pathway |
| spellingShingle | Jia-ming Chen Qiao-yi Huang Wei-hong Chen Jin-xiang Wu Ling-tao Zheng Hui-jie You Yan-chuan Shi Shu Lin Qi-rong Shi Transcriptomics of tissue exosomes to investigate miR-195-5p’s amelioration of endometrial fibrosis via the YAP-Smad7 pathway: an animal study Journal of Translational Medicine Tissue exosomes miR-195-5p Intrauterine adhesion Myofibroblast transdifferentiation YAP–Smad7 Hippo pathway |
| title | Transcriptomics of tissue exosomes to investigate miR-195-5p’s amelioration of endometrial fibrosis via the YAP-Smad7 pathway: an animal study |
| title_full | Transcriptomics of tissue exosomes to investigate miR-195-5p’s amelioration of endometrial fibrosis via the YAP-Smad7 pathway: an animal study |
| title_fullStr | Transcriptomics of tissue exosomes to investigate miR-195-5p’s amelioration of endometrial fibrosis via the YAP-Smad7 pathway: an animal study |
| title_full_unstemmed | Transcriptomics of tissue exosomes to investigate miR-195-5p’s amelioration of endometrial fibrosis via the YAP-Smad7 pathway: an animal study |
| title_short | Transcriptomics of tissue exosomes to investigate miR-195-5p’s amelioration of endometrial fibrosis via the YAP-Smad7 pathway: an animal study |
| title_sort | transcriptomics of tissue exosomes to investigate mir 195 5p s amelioration of endometrial fibrosis via the yap smad7 pathway an animal study |
| topic | Tissue exosomes miR-195-5p Intrauterine adhesion Myofibroblast transdifferentiation YAP–Smad7 Hippo pathway |
| url | https://doi.org/10.1186/s12967-024-05871-8 |
| work_keys_str_mv | AT jiamingchen transcriptomicsoftissueexosomestoinvestigatemir1955psameliorationofendometrialfibrosisviatheyapsmad7pathwayananimalstudy AT qiaoyihuang transcriptomicsoftissueexosomestoinvestigatemir1955psameliorationofendometrialfibrosisviatheyapsmad7pathwayananimalstudy AT weihongchen transcriptomicsoftissueexosomestoinvestigatemir1955psameliorationofendometrialfibrosisviatheyapsmad7pathwayananimalstudy AT jinxiangwu transcriptomicsoftissueexosomestoinvestigatemir1955psameliorationofendometrialfibrosisviatheyapsmad7pathwayananimalstudy AT lingtaozheng transcriptomicsoftissueexosomestoinvestigatemir1955psameliorationofendometrialfibrosisviatheyapsmad7pathwayananimalstudy AT huijieyou transcriptomicsoftissueexosomestoinvestigatemir1955psameliorationofendometrialfibrosisviatheyapsmad7pathwayananimalstudy AT yanchuanshi transcriptomicsoftissueexosomestoinvestigatemir1955psameliorationofendometrialfibrosisviatheyapsmad7pathwayananimalstudy AT shulin transcriptomicsoftissueexosomestoinvestigatemir1955psameliorationofendometrialfibrosisviatheyapsmad7pathwayananimalstudy AT qirongshi transcriptomicsoftissueexosomestoinvestigatemir1955psameliorationofendometrialfibrosisviatheyapsmad7pathwayananimalstudy |