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한빛사논문
- 조회181
Clin. Mol. Hepatol., Jan 22 2025, | https://doi.org/10.3350/cmh.2024.0741
Modulation of PRL-1 within placental MSCs instigates the transition between EMT and MET subsequent to hepatic fibrosis
Jae Yeon Kim1,2, Hyeri Park1,2, Soo Young Park1, Se Ho Kim1, Ja Yun Lim4, Ki Seog Lee5, Si Hyun Bae6, Gi Jin Kim1,2,3
1Department of Biomedical Science, CHA University, Seongnam, 13488, Republic of Korea
2Research Institute of Placental Science, CHA University, Seongnam 13488, Republic of Korea
3Advanced PLAB, PLABiologics Co., Ltd., Seongnam 13488, Republic of Korea
4Department of Integrated Biomedical and Life Sciences, College of Health Science, Korea University, Seoul 02841, Republic of Korea
5Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Republic of Korea
6Department of Internal Medicine, Catholic University Medical College, Seoul 06591, Republic of Korea
Correspondence : Gi Jin Kim
1Department of Biomedical Science, CHA University, Seongnam, 13488, Republic of Korea
2Research Institute of Placental Science, CHA University, Seongnam 13488, Republic of Korea
3Advanced PLAB, PLABiologics Co., Ltd., Seongnam 13488, Republic of Korea
4Department of Integrated Biomedical and Life Sciences, College of Health Science, Korea University, Seoul 02841, Republic of Korea
5Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Republic of Korea
6Department of Internal Medicine, Catholic University Medical College, Seoul 06591, Republic of Korea
Correspondence : Gi Jin Kim
Abstract
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 ligation (BDL)-induced 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 (MET). These findings highlight the therapeutic potential of engineered MSCs for liver disease and suggest innovative strategies for future stem cell therapies.
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 ligation (BDL)-induced 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 (MET). These findings highlight the therapeutic potential of engineered MSCs for liver disease and suggest innovative strategies for future stem cell therapies.
논문정보
- Research article
- 2025년 01월 (BRIC 등록일 2025-01-27)
- 국내 연구진
- 생명과학 > 분자생물학
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