Modulation of phosphatase of regenerating liver-1 within placental mesenchymal stem cells instigates the transition between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition subsequent to hepatic fibrosis
Background/Aims Epithelial-to-mesenchymal transition (EMT) plays a crucial role in hepatic fibrogenesis and liver repair in chronic liver disease. Our research highlights the antifibrotic potential of placenta-derived mesenchymal stem cells (PD-MSCs) and the role of phosphatase of regenerating liver...
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| Format: | Article |
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Korean Association for the Study of the Liver
2025-07-01
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| Series: | Clinical and Molecular Hepatology |
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| Online Access: | http://e-cmh.org/upload/pdf/cmh-2024-0741.pdf |
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| author | Jae Yeon Kim Hyeri Park Soo Young Park Se Ho Kim Ja Yun Lim Ki Seog Lee Si Hyun Bae Gi Jin Kim |
| author_facet | Jae Yeon Kim Hyeri Park Soo Young Park Se Ho Kim Ja Yun Lim Ki Seog Lee Si Hyun Bae Gi Jin Kim |
| author_sort | Jae Yeon Kim |
| collection | DOAJ |
| description | Background/Aims Epithelial-to-mesenchymal transition (EMT) plays a crucial role in hepatic fibrogenesis and liver repair in chronic liver disease. Our research highlights the antifibrotic potential of placenta-derived mesenchymal stem cells (PD-MSCs) and the role of phosphatase of regenerating liver-1 (PRL-1) in promoting liver regeneration. Methods We evaluated the efficacy of PD-MSCs overexpressing PRL-1 (PD-MSCsPRL-1) in a bile duct ligationinduced rat injury model, focusing on their ability to regulate EMT. Results PD-MSCsPRL-1 significantly reduced mesenchymal markers by downregulating TGFB1/SMAD2, outperforming naïve PD-MSCs. The transplantation of PD-MSCsPRL-1 enhanced BMP7/SMAD1/5 expression, promoting epithelial marker expression and stimulating BMP7 within hepatocytes, modulating downstream SMAD signaling. Importantly, further validation confirmed that PRL-1 directly interacts with BMP7 in hepatocytes. Conclusions PRL-1 expression in PD-MSCsPRL-1 restores TGFB1/BMP7 balance, promoting hepatic regeneration through mesenchymal-to-epithelial transition. These findings highlight the therapeutic potential of engineered MSCs for liver disease and suggest innovative strategies for future stem cell therapies. |
| format | Article |
| id | doaj-art-e0545ed7584e4201a56a828f817a018e |
| institution | DOAJ |
| issn | 2287-2728 2287-285X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Korean Association for the Study of the Liver |
| record_format | Article |
| series | Clinical and Molecular Hepatology |
| spelling | doaj-art-e0545ed7584e4201a56a828f817a018e2025-08-20T03:17:26ZengKorean Association for the Study of the LiverClinical and Molecular Hepatology2287-27282287-285X2025-07-0131382384010.3350/cmh.2024.07412152Modulation of phosphatase of regenerating liver-1 within placental mesenchymal stem cells instigates the transition between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition subsequent to hepatic fibrosisJae Yeon Kim0Hyeri Park1Soo Young Park2Se Ho Kim3Ja Yun Lim4Ki Seog Lee5Si Hyun Bae6Gi Jin Kim7 Department of Biomedical Science, CHA University, Seongnam, Korea Department of Biomedical Science, CHA University, Seongnam, Korea Department of Biomedical Science, CHA University, Seongnam, Korea Department of Biomedical Science, CHA University, Seongnam, Korea Department of Integrated Biomedical and Life Sciences, College of Health Science, Korea University, Seoul, Korea Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, Korea Department of Internal Medicine, Catholic University Medical College, Seoul, Korea Department of Biomedical Science, CHA University, Seongnam, KoreaBackground/Aims Epithelial-to-mesenchymal transition (EMT) plays a crucial role in hepatic fibrogenesis and liver repair in chronic liver disease. Our research highlights the antifibrotic potential of placenta-derived mesenchymal stem cells (PD-MSCs) and the role of phosphatase of regenerating liver-1 (PRL-1) in promoting liver regeneration. Methods We evaluated the efficacy of PD-MSCs overexpressing PRL-1 (PD-MSCsPRL-1) in a bile duct ligationinduced rat injury model, focusing on their ability to regulate EMT. Results PD-MSCsPRL-1 significantly reduced mesenchymal markers by downregulating TGFB1/SMAD2, outperforming naïve PD-MSCs. The transplantation of PD-MSCsPRL-1 enhanced BMP7/SMAD1/5 expression, promoting epithelial marker expression and stimulating BMP7 within hepatocytes, modulating downstream SMAD signaling. Importantly, further validation confirmed that PRL-1 directly interacts with BMP7 in hepatocytes. Conclusions PRL-1 expression in PD-MSCsPRL-1 restores TGFB1/BMP7 balance, promoting hepatic regeneration through mesenchymal-to-epithelial transition. These findings highlight the therapeutic potential of engineered MSCs for liver disease and suggest innovative strategies for future stem cell therapies.http://e-cmh.org/upload/pdf/cmh-2024-0741.pdfepithelial-mesenchymal transitionliver diseasesmesenchymal stem cell transplantationprotein tyrosine phosphatases |
| spellingShingle | Jae Yeon Kim Hyeri Park Soo Young Park Se Ho Kim Ja Yun Lim Ki Seog Lee Si Hyun Bae Gi Jin Kim Modulation of phosphatase of regenerating liver-1 within placental mesenchymal stem cells instigates the transition between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition subsequent to hepatic fibrosis Clinical and Molecular Hepatology epithelial-mesenchymal transition liver diseases mesenchymal stem cell transplantation protein tyrosine phosphatases |
| title | Modulation of phosphatase of regenerating liver-1 within placental mesenchymal stem cells instigates the transition between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition subsequent to hepatic fibrosis |
| title_full | Modulation of phosphatase of regenerating liver-1 within placental mesenchymal stem cells instigates the transition between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition subsequent to hepatic fibrosis |
| title_fullStr | Modulation of phosphatase of regenerating liver-1 within placental mesenchymal stem cells instigates the transition between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition subsequent to hepatic fibrosis |
| title_full_unstemmed | Modulation of phosphatase of regenerating liver-1 within placental mesenchymal stem cells instigates the transition between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition subsequent to hepatic fibrosis |
| title_short | Modulation of phosphatase of regenerating liver-1 within placental mesenchymal stem cells instigates the transition between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition subsequent to hepatic fibrosis |
| title_sort | modulation of phosphatase of regenerating liver 1 within placental mesenchymal stem cells instigates the transition between epithelial to mesenchymal transition and mesenchymal to epithelial transition subsequent to hepatic fibrosis |
| topic | epithelial-mesenchymal transition liver diseases mesenchymal stem cell transplantation protein tyrosine phosphatases |
| url | http://e-cmh.org/upload/pdf/cmh-2024-0741.pdf |
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