title: Activation of the Jak/Stat signalling pathway by leukaemia inhibitory factor stimulates trans-differentiation of human non-endocrine pancreatic cells into insulin-producing cells.
abstract: 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.
authors: Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors: T
authors: T
authors: Koblas
authors: I
authors: I
authors: Leontovyč
authors: K
authors: K
authors: Zacharovová
authors: Z
authors: Z
authors: Berková
authors: J
authors: J
authors: Kříž
authors: P
authors: P
authors: Girman
authors: F
authors: F
authors: Saudek
mesh_terms: D002096:C-Peptide; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000166:cytology*; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology*; D010179:Pancreas / Q000166:cytology*; D000073718:Pancreatitis-Associated Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002096:C-Peptide; D053605:Leukemia Inhibitory Factor; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D050791:STAT Transcription Factors; D053612:Janus Kinases