title: Control of Schwann cell survival and proliferation: autocrine factors and neuregulins.
abstract: Postnatal rat Schwann cells secrete factors that prevent the programmed cell death (PCD) of low-density Schwann cells in serum-free culture. These autocrine survival signal(s) do not promote Schwann cell proliferation. Moreover, while NRG and bFGF, which promote proliferation, both rescue a subpopulation of neonatal Schwann cells from PCD, they do not rescue freshly isolated Schwann cells from older animals; other known protein factors tested also do not mimic the autocrine signal. These results suggest that Schwann cells switch their survival dependency around the time of birth from axonal signals such as NRG to autocrine signals. Such an arrangement would be advantageous for the regeneration of peripheral axons following injury. We also compared NRG-induced Schwann cell proliferation using autocrine signals or serum to promote survival. The autocrine signals increase the rate of NRG-stimulated proliferation of low-density Schwann cells in serum-free medium, whereas serum inhibits proliferation by inhibiting both the production of survival signals and the expression of erbB2 and erbB3 receptors; these inhibitions are all reversed by forskolin. In contrast, forskolin has no effect on proliferation when the cells are exposed to high levels of autocrine factors.
authors.affiliation: Department of Biology, Eisai London Research, University College London, Gower Street, London, WC1E 6BT, United Kingdom.
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: F S
authors.initials: FS
authors.lastname: Esch
authors.forename: M A
authors.initials: MA
authors.lastname: Marchionni
authors.forename: A W
authors.initials: AW
authors.lastname: Mudge
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000502:physiology; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D020904:Glia Maturation Factor; D006023:Glycoproteins / Q000502:physiology; D006131:Growth Inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000502:physiology; D007797:Laminin / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D020880:Neuregulins; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D020893:Receptor, ErbB-3; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
chemical_list: D005576:Colforsin; D017077:Culture Media, Conditioned; D016207:Cytokines; D066246:ErbB Receptors; D016222:Fibroblast Growth Factor 2; D020904:Glia Maturation Factor; D006023:Glycoproteins; D006131:Growth Inhibitors; D006133:Growth Substances; D007797:Laminin; D008934:Mitogens; D009419:Nerve Tissue Proteins; D020880:Neuregulins; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3