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-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.
Demeterco
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Whittier Institute and Department of Pediatrics, University of California at San Diego, La Jolla 92037, USA.
Beattie
G M
GM
Dib
S A
SA
Lopez
A D
AD
Hayek
A
A
D028341:Activins; D066259:Betacellulin; D002454:Cell Differentiation; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007265:Inhibins / Q000502:physiology*; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D018613:Microscopy, Confocal; D010179:Pancreas / Q000166:cytology / Q000196:embryology / Q000254:growth & development*
C587851:BTC protein, human; D066259:Betacellulin; D006133:Growth Substances; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D028341:Activins; D007265:Inhibins; D004247:DNA