hAMSCs regulate EMT in the progression of experimental pulmonary fibrosis through delivering miR-181a-5p targeting TGFBR1
Abstract Background Pulmonary fibrosis (PF) is a common and multidimensional devastating interstitial lung disease. The development of novel and more effective interventions for PF is an urgent clinical need. A previous study has found that miR-181a-5p plays an important role in the development of P...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-024-04095-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544923156840448 |
|---|---|
| author | Yanyang Wang Chan Liu Nuoxin Wang Dong Weng Yan Zhao Hongyu Yang Haoyuan Wang Shangfu Xu Jianmei Gao Changhui Lang Zhenhai Fan Limei Yu Zhixu He |
| author_facet | Yanyang Wang Chan Liu Nuoxin Wang Dong Weng Yan Zhao Hongyu Yang Haoyuan Wang Shangfu Xu Jianmei Gao Changhui Lang Zhenhai Fan Limei Yu Zhixu He |
| author_sort | Yanyang Wang |
| collection | DOAJ |
| description | Abstract Background Pulmonary fibrosis (PF) is a common and multidimensional devastating interstitial lung disease. The development of novel and more effective interventions for PF is an urgent clinical need. A previous study has found that miR-181a-5p plays an important role in the development of PF, and human amniotic mesenchymal stem cells (hAMSCs) exert potent therapeutic potential on PF. However, whether hAMSCs act on PF by delivering miR-181a-5p and its detailed mechanism still remain unknown. Thus, this study was designed to investigate the underlying possible mechanism of hAMSCs on PF in bleomycin (BLM)-induced mouse PF model, and a co-culture system of hAMSCs and A549 cells epithelial mesenchymal transition (EMT) model, focusing on its effects on collagen deposition, EMT, and epithelial cell cycle regulation. Methods hAMSCs with different miR-181a-5p expression levels were constructed. BLM (4 mg/kg) was used to create a PF model, while TGF-β1 was used to induce A549 cells to construct an EMT model. Furthermore, the effects of different miR-181a-5p expression in hAMSCs on collagen deposition and EMT during lung fibrosis were assessed in vivo and in vitro. Results We found that hAMSCs exerted anti-fibrotic effect in BLM-induced mouse PF model. Moreover, hAMSCs also exerted protective effect on TGFβ1-induced A549 cell EMT model. Furthermore, hAMSCs ameliorated PF by promoting epithelial cell proliferation, reducing epithelial cell apoptosis, and attenuating EMT of epithelial cells through paracrine effects. hAMSCs regulated EMT in PF through delivering miR-181a-5p targeting TGFBR1. Conclusions Our findings reveal for the first time that hAMSCs inhibit PF by promoting epithelial cell proliferation, reducing epithelial cell apoptosis, and attenuating EMT. Mechanistically, the therapeutic effect of hMASCs on PF is achieved through delivering miR-181a-5p targeting TGFBR1. |
| format | Article |
| id | doaj-art-38e6a178aa86492db5ab5b7c9b7cfc1c |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-38e6a178aa86492db5ab5b7c9b7cfc1c2025-01-12T12:10:22ZengBMCStem Cell Research & Therapy1757-65122025-01-0116112210.1186/s13287-024-04095-3hAMSCs regulate EMT in the progression of experimental pulmonary fibrosis through delivering miR-181a-5p targeting TGFBR1Yanyang Wang0Chan Liu1Nuoxin Wang2Dong Weng3Yan Zhao4Hongyu Yang5Haoyuan Wang6Shangfu Xu7Jianmei Gao8Changhui Lang9Zhenhai Fan10Limei Yu11Zhixu He12Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical UniversityKey Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical UniversityKey Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical UniversityKey Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical UniversityDepartment of Prevention Healthcare, Southwest Hospital, First Affiliated Hospital of the Army Medical UniversityKey Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical UniversityDepartment of Cardiothoracic Surgery, Liuzhou People’s HospitalKey Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical UniversityKey Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of EducationDepartment of Pediatrics, Affiliated Hospital of Zunyi Medical UniversityKey Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical UniversityKey Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical UniversityCenter of Tissue Engineering and Stem Cell Research, Guizhou Medical UniversityAbstract Background Pulmonary fibrosis (PF) is a common and multidimensional devastating interstitial lung disease. The development of novel and more effective interventions for PF is an urgent clinical need. A previous study has found that miR-181a-5p plays an important role in the development of PF, and human amniotic mesenchymal stem cells (hAMSCs) exert potent therapeutic potential on PF. However, whether hAMSCs act on PF by delivering miR-181a-5p and its detailed mechanism still remain unknown. Thus, this study was designed to investigate the underlying possible mechanism of hAMSCs on PF in bleomycin (BLM)-induced mouse PF model, and a co-culture system of hAMSCs and A549 cells epithelial mesenchymal transition (EMT) model, focusing on its effects on collagen deposition, EMT, and epithelial cell cycle regulation. Methods hAMSCs with different miR-181a-5p expression levels were constructed. BLM (4 mg/kg) was used to create a PF model, while TGF-β1 was used to induce A549 cells to construct an EMT model. Furthermore, the effects of different miR-181a-5p expression in hAMSCs on collagen deposition and EMT during lung fibrosis were assessed in vivo and in vitro. Results We found that hAMSCs exerted anti-fibrotic effect in BLM-induced mouse PF model. Moreover, hAMSCs also exerted protective effect on TGFβ1-induced A549 cell EMT model. Furthermore, hAMSCs ameliorated PF by promoting epithelial cell proliferation, reducing epithelial cell apoptosis, and attenuating EMT of epithelial cells through paracrine effects. hAMSCs regulated EMT in PF through delivering miR-181a-5p targeting TGFBR1. Conclusions Our findings reveal for the first time that hAMSCs inhibit PF by promoting epithelial cell proliferation, reducing epithelial cell apoptosis, and attenuating EMT. Mechanistically, the therapeutic effect of hMASCs on PF is achieved through delivering miR-181a-5p targeting TGFBR1.https://doi.org/10.1186/s13287-024-04095-3Amniotic membrane mesenchymal stem cellshAMSCsPulmonary fibrosisEpithelial mesenchymal transitionmiR-181a-5pTGFBR1 |
| spellingShingle | Yanyang Wang Chan Liu Nuoxin Wang Dong Weng Yan Zhao Hongyu Yang Haoyuan Wang Shangfu Xu Jianmei Gao Changhui Lang Zhenhai Fan Limei Yu Zhixu He hAMSCs regulate EMT in the progression of experimental pulmonary fibrosis through delivering miR-181a-5p targeting TGFBR1 Stem Cell Research & Therapy Amniotic membrane mesenchymal stem cells hAMSCs Pulmonary fibrosis Epithelial mesenchymal transition miR-181a-5p TGFBR1 |
| title | hAMSCs regulate EMT in the progression of experimental pulmonary fibrosis through delivering miR-181a-5p targeting TGFBR1 |
| title_full | hAMSCs regulate EMT in the progression of experimental pulmonary fibrosis through delivering miR-181a-5p targeting TGFBR1 |
| title_fullStr | hAMSCs regulate EMT in the progression of experimental pulmonary fibrosis through delivering miR-181a-5p targeting TGFBR1 |
| title_full_unstemmed | hAMSCs regulate EMT in the progression of experimental pulmonary fibrosis through delivering miR-181a-5p targeting TGFBR1 |
| title_short | hAMSCs regulate EMT in the progression of experimental pulmonary fibrosis through delivering miR-181a-5p targeting TGFBR1 |
| title_sort | hamscs regulate emt in the progression of experimental pulmonary fibrosis through delivering mir 181a 5p targeting tgfbr1 |
| topic | Amniotic membrane mesenchymal stem cells hAMSCs Pulmonary fibrosis Epithelial mesenchymal transition miR-181a-5p TGFBR1 |
| url | https://doi.org/10.1186/s13287-024-04095-3 |
| work_keys_str_mv | AT yanyangwang hamscsregulateemtintheprogressionofexperimentalpulmonaryfibrosisthroughdeliveringmir181a5ptargetingtgfbr1 AT chanliu hamscsregulateemtintheprogressionofexperimentalpulmonaryfibrosisthroughdeliveringmir181a5ptargetingtgfbr1 AT nuoxinwang hamscsregulateemtintheprogressionofexperimentalpulmonaryfibrosisthroughdeliveringmir181a5ptargetingtgfbr1 AT dongweng hamscsregulateemtintheprogressionofexperimentalpulmonaryfibrosisthroughdeliveringmir181a5ptargetingtgfbr1 AT yanzhao hamscsregulateemtintheprogressionofexperimentalpulmonaryfibrosisthroughdeliveringmir181a5ptargetingtgfbr1 AT hongyuyang hamscsregulateemtintheprogressionofexperimentalpulmonaryfibrosisthroughdeliveringmir181a5ptargetingtgfbr1 AT haoyuanwang hamscsregulateemtintheprogressionofexperimentalpulmonaryfibrosisthroughdeliveringmir181a5ptargetingtgfbr1 AT shangfuxu hamscsregulateemtintheprogressionofexperimentalpulmonaryfibrosisthroughdeliveringmir181a5ptargetingtgfbr1 AT jianmeigao hamscsregulateemtintheprogressionofexperimentalpulmonaryfibrosisthroughdeliveringmir181a5ptargetingtgfbr1 AT changhuilang hamscsregulateemtintheprogressionofexperimentalpulmonaryfibrosisthroughdeliveringmir181a5ptargetingtgfbr1 AT zhenhaifan hamscsregulateemtintheprogressionofexperimentalpulmonaryfibrosisthroughdeliveringmir181a5ptargetingtgfbr1 AT limeiyu hamscsregulateemtintheprogressionofexperimentalpulmonaryfibrosisthroughdeliveringmir181a5ptargetingtgfbr1 AT zhixuhe hamscsregulateemtintheprogressionofexperimentalpulmonaryfibrosisthroughdeliveringmir181a5ptargetingtgfbr1 |