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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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Korean Association for the Study of the Liver
2025-07-01
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| Series: | Clinical and Molecular Hepatology |
| Subjects: | |
| Online Access: | http://e-cmh.org/upload/pdf/cmh-2024-0741.pdf |
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| Summary: | 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. |
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| ISSN: | 2287-2728 2287-285X |