
Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(23)
Published: Dec. 1, 2024
The differentiation of mesenchymal stem cells (MSCs) into hepatocyte-like (HLCs) is considered one the most promising strategies for alternative hepatocyte transplantation to treat end-stage liver disease. To advance this method, it crucial gain a deeper understanding mechanisms governing hepatogenic differentiation. study demonstrated that suppression intracellular domain release Notch pathway receptor via γ-secretase inhibitor N-[(3, 5-difluorophenyl)acetyl]-L-alanyl-2-phenylglycine-1, 1-dimethylethyl ester (DAPT) significantly promotes expression hepatocyte-related genes and proteins in HLCs. Increased inducible NO synthase (iNOS) during led elevated endogenous production. Biotin switch assays revealed gradual increase S-nitrosylation (SNO)-NOTCH1 decrease overall NOTCH1 addition exogenous donor S-nitrosoglutathione (GSNO) SNO dithiothreitol (DTT) further SNO-NOTCH1 MSCs mature hepatocytes. Briefly, our results fully modification extracellular by NO, leading formation SNO-NOTCH1, inhibiting signalling pathway. Our highlights critical role regulating offers new insights driving process.
Language: Английский