Activation of the Jak/Stat signalling pathway by leukaemia inhibitory factor stimulates trans-differentiation of human non-endocrine pancreatic cells into insulin-producing cells
Language English Country Czech Republic Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22849859
PII: file/5641/FB2012A0016.pdf
Knihovny.cz E-resources
- MeSH
- Insulin-Secreting Cells cytology MeSH
- Cell Differentiation drug effects MeSH
- C-Peptide MeSH
- Immunohistochemistry MeSH
- Janus Kinases genetics metabolism MeSH
- Cells, Cultured MeSH
- Leukemia Inhibitory Factor pharmacology MeSH
- Humans MeSH
- Pancreas cytology MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Pancreatitis-Associated Proteins MeSH
- Signal Transduction drug effects MeSH
- STAT Transcription Factors genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- C-Peptide MeSH
- Janus Kinases MeSH
- Leukemia Inhibitory Factor MeSH
- Pancreatitis-Associated Proteins MeSH
- REG3A protein, human MeSH Browser
- STAT Transcription Factors MeSH
Differentiation of pancreatic β-cells is regulated by a wide range of signalling pathways. The aim of our current work was to evaluate the effect of the Jak/Stat signalling pathway on the differentiation of human non-endocrine pancreatic cells into insulin-producing cells. Activation of the Jak/Stat signalling pathway by leukaemia inhibitory factor (LIF) stimulated differentiation of C-peptide-negative human non-endocrine pancreatic cells into insulin-producing cells in 6.3 ± 2.0 % cells (N = 5) and induced expression of pro-endocrine transcription factor neurogenin 3, Notch signalling pathway suppressor HES6 and stimulator of β-cell neogenesis REG3A. The expression of the REG3A gene and increased rate of differentiation into insulin-producing cells (10.2 ± 2.1 %) were further stimulated by a combination of LIF with nicotinamide and dexamethasone. Glucose-stimulated (5 vs. 20 mM) C-peptide secretion confirmed proper insulin secretory function of trans-differentiated insulin-producing cells (0.51 vs. 2.03 pmol C-peptide/μg DNA, P < 0.05). Our results indicate that Jak/Stat signalling critically contributes to trans-differentiation of non-endocrine pancreatic cells into functional insulin-producing cells. The positive effect of the Jak/Stat signalling pathway on trans-differentiation is mediated by the key genes that activate differentiation of pancreatic β-cells.