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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Background/Aims The embryonal origin of hepatic stellate cells (HSCs), the principal cells in hepatic fibrogenesis, is still intriguing. We have previously demonstrated that human HSCs express cytokeratins which suggests the epithelial origin of these cells. To further explore the origin and the differentiation of HSCs we studied the expression of E-cadherin, the specific marker of epithelial cells, in human and rat HSCs. Methods: We studied the changing pattern of E-cadherin expression during spontaneous activation of primarily isolated human HSCs by immunofluorescence staining and RT-PCR. To confirm the expression of E-cadherin in HSCs in vivo we performed double immunofluorescence staining for E-cadherin and glial fibrillary acidic protein, the specific identification marker of quiescent rat HSCs, in normal rat liver. Results: Quiescent human HSCs were labeled strongly by anti-E-cadherin monoclonal antibody at the first and seventh days after primary culture. Human HSCs, however, did not stain for E-cadherin after the first passage of culture. RT-PCR also confirmed these modulations of E-cadherin expression. Double immunofluorescence staining, performed on rat liver tissue and observed by confocal laser scanning microscopy, unequivocally revealed the membranous expression of E-cadherin in quiescent HSCs labeled by glial fibrillary acidic protein. Conclusions: Quiescent HSCs of humans and rats express E-cadherin both in vitro and in vivo. The extent of E-cadherin expression rapidly decreases during the process of spontaneous activation. Our results suggest that HSCs may be of epithelial origin and undergo epithelial-mesenchymal transition during activation process.(Korean J Hepatol 2002;8:90-99)
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