Background & Aims: The appearance of hepatic foci in pancreas has been well-documented in animal experiments and in patients with pancreatic cancer. We previously demonstrated that transdifferentiation of pancreatic exocrine cells to hepatocytes required members of the CCAAT enhancer binding protein family. Although the molecular basis of hepatic transdifferentiation is understood, the early cellular events remain to be defined.
Methods: Dexamethasone and oncostatin M were used to induce transdifferentiation of primary cultures of mouse acinar cells and exocrine cell lines into hepatocytes. Fluorescent-activated cell sorting was used to identify intermediate cell types and side-population characteristics. Cre-loxP-based lineage tracing was used to investigate whether acinar cells contribute directly to hepatocytes via intermediates that express adenosine triphosphate-binding cassette subfamily G member 2 (ABCG2).
Results: Lineage tracing studies showed that hepatocytes were derived directly from pancreatic cells via ABCG2-expressing intermediates. Exposure of cells to insulin increased Akt phosphorylation, ABCG2 expression, and hepatic transdifferentiation. Inhibition of the phosphoinositide 3-kinase pathway, through addition of LY294002 or overexpression of a dominant-negative form of Akt, was sufficient to prevent transdifferentiation. When ABCG2-expressing cells were incubated with glucagon-like-peptide 1 or epidermal growth factor, the intermediate cells could differentiate into insulin-producing beta-like cells.
Conclusions: The phosphoinositide 3-kinase pathway is important in the transdifferentiation of acinar cells to hepatocytes and those hepatocytes arise from acinar cells via ABCG2-expressing intermediates. Furthermore, ABCG2-expressing cells are multipotent and able to differentiate into hepatocytes and insulin-producing beta cells.
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http://dx.doi.org/10.1053/j.gastro.2010.02.011 | DOI Listing |
Pathol Int
January 2025
Department of Cancer Pathology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
Recent studies suggest that lung adenocarcinoma cells are closely associated with the tumorigenesis of large-cell neuroendocrine carcinoma via cellular transformation. However, morphological evidence, along with genetic abnormalities before, during, and after transformation, is quite limited. We present here a case of combined large-cell neuroendocrine carcinoma and adenocarcinoma exhibiting acinar and solid patterns.
View Article and Find Full Text PDFJ Exp Biol
January 2025
Division of Cell Structure, National Institute for Physiological Sciences, Okazaki, Aichi 444-8787, Japan.
We investigated the extracellular and intracellular digestion of bivalves employing magnetic resonance imaging (MRI). Ruditapes philippinarum clams and Mytilus galloprovincialis mussels were incubated in seawater containing a contrast reagent (GdDTPA) at 20°C. The digestive systems, from the esophagus to the rectum, were visualized at a high signal intensity by the T1-weighted MRI.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen, China; Xiamen Key Laboratory of Chiral Drugs, Xiamen, China. Electronic address:
Ethnopharmacological Relevance: Pseudostellaria heterophylla (Tài Zǐ Shēn, TZS) is a traditional Chinese medicine with spleen and qi benefits. Its immunomodulatory, anti-fatigue, anti-stress, and lipid metabolism regulation effects have been clinically confirmed, but its role in meibomian gland dysfunction (MGD) is still unclear.
Aim Of The Study: This study aims to investigate the effect and mechanism of action of TZS in treating MGD.
Pharmacol Res
January 2025
Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu, China. Electronic address:
The necrosis of pancreatic acinar cells is a key molecular event in the progression of acute pancreatitis (AP), with disturbances in mitochondrial energy metabolism considered to be a direct causative factor of acinar cell necrosis. Histidine triad nucleotide-binding protein 2 (HINT2) has been implicated in the development of various diseases, whereas its involvement in the progression of AP remains unclear. This study aims to investigate the role of HINT2 in AP.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes and Metabolism Research Institute, Duarte, USA.
Lectins are produced in almost all life forms, can interact with targets (glycans) in a cross-kingdom manner and have served as valuable tools for studying glycobiology. Previously, a bacterial lectin, named Streptomyces hemagglutinin (SHA), was found to agglutinate human type B erythrocytes. However, the binding of SHA to mammalian cell types other than human erythrocytes has not been explored.
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