A role for activin A and betacellulin in human fetal pancreatic cell differentiation and growth

Activin A (Act.A), a member of the transforming growth factor beta family of secreted proteins, has been implicated in the regulation of growth and differentiation of various cell types. Betacellulin (BTC), a member of the epidermal growth factor family, converts exocrine AR42J cells to insulin-expr...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2000-10, Vol.85 (10), p.3892-3897
Main Authors: DEMETERCO, Carla, BEATTIE, Gillian M, DIB, Sergio Atala, LOPEZ, Ana D, HAYEK, Alberto
Format: Article
Language:English
Subjects:
Activins
Betacellulin
Biological and medical sciences
Cell Differentiation
Cell Division - physiology
Cells, Cultured
DNA - biosynthesis
Embryology: invertebrates and vertebrates. Teratology
Fundamental and applied biological sciences. Psychology
Growth Substances - physiology
Humans
Immunohistochemistry
Inhibins - physiology
Insulin - biosynthesis
Insulin - metabolism
Intercellular Signaling Peptides and Proteins
Microscopy, Confocal
Organogenesis. Fetal development
Organogenesis. Physiological fonctions
Pancreas - cytology
Pancreas - embryology
Pancreas - growth & development
Tropical medicine
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Summary:Activin A (Act.A), a member of the transforming growth factor beta family of secreted proteins, has been implicated in the regulation of growth and differentiation of various cell types. Betacellulin (BTC), a member of the epidermal growth factor family, converts exocrine AR42J cells to insulin-expressing cells when combined with Act.A. We have used primary cultures of human fetal pancreatic tissue to identify the effects of Act.A and/or BTC on islet development and growth. Exposure to Act.A resulted in a 1.5-fold increase in insulin content (P < 0.005) and a 2-fold increase in the number of cells immunopositive for insulin (P < 0.005). The formation of islet-like cell clusters, containing mainly epithelial cells, during a 5-day culture, was stimulated 1.4-fold by BTC (P < 0.05). BTC alone caused a 2.6-fold increase in DNA synthesis (P < 0.005). These data suggest that Act.A induces endocrine differentiation, whereas BTC has a mitogenic effect on human undifferentiated pancreatic epithelial cells.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.85.10.3892