Modulation of PRL-1 within placental MSCs instigates the transition between EMT and MET subsequent to hepatic fibrosis

Kim, Jae Yeon; Park, Hyeri; Park, Soo Young; Kim, Se Ho; Lim, Ja Yun; Lee, Ki Seog; Bae, Si Hyun; Kim, Gi Jin

doi:.0..

Original Article

Modulation of PRL-1 within placental MSCs instigates the transition between EMT and MET subsequent to hepatic fibrosis

Jae Yeon Kim^1,2, Hyeri Park^1,2, Soo Young Park¹, Se Ho Kim¹, Ja Yun Lim⁴, Ki Seog Lee⁵, Si Hyun Bae⁶, Gi Jin Kim^1,2,3

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 ,
Tel: +82-31-881-7145, Fax: +82-31-881-7249, Email: gjkim@cha.ac.kr

Received: September 12, 2024 Revised: January 7, 2025 Accepted: January 20, 2025

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-MSCs^PRL-1) in a bile duct ligation (BDL)-induced rat injury model, focusing on their ability to regulate EMT.
Results
PD-MSCs^PRL-1 significantly reduced mesenchymal markers by downregulating TGFB1/SMAD2, outperforming naïve PD-MSCs. The transplantation of PD-MSCs^PRL-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-MSCs^PRL-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.

KeyWords: EMT/MET, PRL-1, Engineered MSC therapy, Liver disease