1. Protein tyrosine phosphatase of liver regeneration-1 is required for normal timing of cell cycle progression during liver regeneration.
- Author
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Jiao Y, Ye DZ, Li Z, Teta-Bissett M, Peng Y, Taub R, Greenbaum LE, and Kaestner KH
- Subjects
- Animals, Cell Division physiology, Cell Proliferation genetics, Cell Proliferation physiology, Hepatectomy methods, Hepatocytes pathology, Liver metabolism, Male, Mice, Mice, Transgenic, Signal Transduction genetics, Time Factors, Cell Cycle, Hepatocytes metabolism, Immediate-Early Proteins genetics, Liver Regeneration genetics, Mutation genetics, Protein Tyrosine Phosphatases genetics
- Abstract
Protein tyrosine phosphatase of liver regeneration-1 (Prl-1) is an immediate-early gene that is significantly induced during liver regeneration. Several in vitro studies have suggested that Prl-1 is important for the regulation of cell cycle progression. To evaluate its function in liver regeneration, we ablated the Prl-1 gene specifically in mouse hepatocytes using the Cre-loxP system. Prl-1 mutant mice (Prl-1(loxP/loxP);AlfpCre) appeared normal and fertile. Liver size and metabolic function in Prl-1 mutants were comparable to controls, indicating that Prl-1 is dispensable for liver development, postnatal growth, and hepatocyte differentiation. Mutant mice demonstrated a delay in DNA synthesis after 70% partial hepatectomy, although ultimate liver mass restoration was not affected. At 40 h posthepatectomy, reduced protein levels of the cell cycle regulators cyclin E, cyclin A2, cyclin B1, and cyclin-dependent kinase 1 were observed in Prl-1 mutant liver. Investigation of the major signaling pathways involved in liver regeneration demonstrated that phosphorylation of protein kinase B (AKT) and signal transducer and activator of transcription (STAT) 3 were significantly reduced at 40 h posthepatectomy in Prl-1 mutants. Taken together, this study provides evidence that Prl-1 is required for proper timing of liver regeneration after partial hepatectomy. Prl-1 promotes G1/S progression via modulating expression of several cell cycle regulators through activation of the AKT and STAT3 signaling pathway., (Copyright © 2015 the American Physiological Society.)
- Published
- 2015
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