Amphiregulin acts as an autocrine survival factor for adult sensory neurons.
We studied the effect of amphiregulin on axonal outgrowth and survival in sensory neurons in organ cultured and dissociated mouse dorsal root ganglia (DRG). Amphiregulin at 20 ng/ml stimulated axonal outgrowth in both preparations. The EGF receptor inhibitor AG1478 inhibited outgrowth at 10 microM but not at 1 microM, where it abolished the stimulatory effects of amphiregulin. Fluoro-Jade staining and neuronal counting showed that more neurons survived in culture in the presence of amphiregulin while AG1478 at 10 microM but not 1 microM increased cell death. Small and medium sized neurons were immunopositive for both amphiregulin and the EGF receptor. Taken together these results suggest that amphiregulin can act as an autocrine survival factor for sensory neurons and stimulate axonal outgrowth through the EGF receptor.
Nilsson
Anna
A
Department of Cell and Organism Biology, Lund University, Helgona v 3 B, S-223 62 Lund, Sweden. Anna.Nilsson@COB.lu.se
Kanje
Martin
M
D066258:Amphiregulin; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066255:EGF Family of Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology*; D006023:Glycoproteins / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D051379:Mice; D009475:Neurons, Afferent / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D011799:Quinazolines; D020032:Tyrphostins / Q000494:pharmacology
D066258:Amphiregulin; C587849:Areg protein, mouse; D066255:EGF Family of Proteins; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D066246:ErbB Receptors