Non-antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re-differentiation.
The expression of myelination-associated genes (MGs) can be induced by cyclic adenosine monophosphate (cAMP) elevation in isolated Schwann cells (SCs). To further understand the effect of known SC mitogens in the regulation of SC differentiation, we studied the response of SCs isolated from adult nerves to combined cAMP, growth factors, including neuregulin, and serum. In adult SCs, the induction of MGs by cAMP coincided with the loss of genes expressed in non-myelin-forming SCs and with a change in cell morphology from a bipolar to an expanded epithelial-like shape. Prolonged treatment with high doses of cAMP-stimulating agents, as well as low cell density, was required for the induction of SC differentiation. Stimulation with serum, neuregulin alone, or other growth factors including PDGF, IGF and FGF, increased SC proliferation but did not induce the expression of MGs or the associated morphological change. Most importantly, when these factors were administered in combination with cAMP-stimulating agents, SC proliferation was synergistically increased without reducing the differentiating activity of cAMP. Even though the initiation of DNA synthesis and the induction of differentiation were mostly incompatible events in individual cells, SCs were able to differentiate under conditions that also supported active proliferation. Overall, the results indicate that in the absence of neurons, cAMP can trigger SC re-differentiation concurrently with, but independently of, growth factor signaling.
Monje
Paula V
PV
The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA. mpaula@miamiproject.med.miami.edu
Rendon
Sayuri
S
Athauda
Gagani
G
Bates
Margaret
M
Wood
Patrick M
PM
Bunge
Mary Bartlett
MB
D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D000242:Cyclic AMP / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005727:Ganglia, Spinal / Q000502:physiology; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009186:Myelin Sheath / Q000235:genetics*; D020880:Neuregulins / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology*; D044967:Serum / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; D020880:Neuregulins; D010982:Platelet-Derived Growth Factor; D005346:Fibroblast Growth Factors; D004247:DNA; D000242:Cyclic AMP