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

IF 14 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Clinical and Molecular Hepatology Pub Date : 2025-01-22 DOI:10.3350/cmh.2024.0741

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

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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.

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胎盘间充质干细胞中PRL-1的调节促进了肝纤维化后EMT和MET之间的转变。

背景/目的：上皮-间质转化（Epithelial-to-mesenchymal transition， EMT）在慢性肝病的肝纤维化和肝脏修复中起着至关重要的作用。我们的研究强调了胎盘来源的间充质干细胞（PD-MSCs）的抗纤维化潜力以及再生肝脏磷酸酶-1 （PRL-1）在促进肝脏再生中的作用。方法：我们评估过表达PRL-1的PD-MSCs （PD-MSCsPRL-1）在胆管结扎（BDL）诱导的大鼠损伤模型中的作用，重点关注其调节EMT的能力。结果：PD-MSCsPRL-1通过下调TGFB1/SMAD2显著降低间充质标志物，优于naïve PD-MSCs。PD-MSCsPRL-1的移植增强了BMP7/SMAD1/5的表达，促进了上皮标志物的表达，刺激了肝细胞内的BMP7，调节了下游SMAD信号。重要的是，进一步的验证证实了PRL-1在肝细胞中直接与BMP7相互作用。结论：PRL-1在PD-MSCsPRL-1中的表达可恢复TGFB1/BMP7平衡，通过间充质-上皮转化（MET）促进肝脏再生。这些发现突出了工程化间充质干细胞治疗肝脏疾病的潜力，并为未来干细胞治疗提出了创新策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and Molecular Hepatology Medicine-Hepatology

CiteScore

15.60

自引率

9.00%

发文量

审稿时长

10 weeks

期刊介绍： Clinical and Molecular Hepatology is an internationally recognized, peer-reviewed, open-access journal published quarterly in English. Its mission is to disseminate cutting-edge knowledge, trends, and insights into hepatobiliary diseases, fostering an inclusive academic platform for robust debate and discussion among clinical practitioners, translational researchers, and basic scientists. With a multidisciplinary approach, the journal strives to enhance public health, particularly in the resource-limited Asia-Pacific region, which faces significant challenges such as high prevalence of B viral infection and hepatocellular carcinoma. Furthermore, Clinical and Molecular Hepatology prioritizes epidemiological studies of hepatobiliary diseases across diverse regions including East Asia, North Asia, Southeast Asia, Central Asia, South Asia, Southwest Asia, Pacific, Africa, Central Europe, Eastern Europe, Central America, and South America. The journal publishes a wide range of content, including original research papers, meta-analyses, letters to the editor, case reports, reviews, guidelines, editorials, and liver images and pathology, encompassing all facets of hepatology.