title: Human neuroma contains increased levels of semaphorin 3A, which surrounds nerve fibers and reduces neurite extension in vitro.
abstract: Neuroma formation after peripheral nerve injury is detrimental to functional recovery and is therefore a significant clinical problem. The molecular basis for this phenomenon is not fully understood. Here, we show that the expression of the chemorepulsive protein semaphorin 3A (sema3A), but not semaphorin 3F, is increased in human neuroma tissue that has formed in severe obstetric brachial plexus lesions. Sema3A is produced by fibroblasts in the epineurial space and appears to be secreted into the extracellular matrix. It surrounds fascicles, minifascicles, or single axons, suggesting a role in fasciculation and inhibition of neurite outgrowth. Lentiviral vector-mediated knock-down of Neuropilin 1, the receptor for sema3A, leads to increased neurite outgrowth of F11 cells cultured on neuroma tissue, but not of F11 cells cultured on normal nerve tissue. These findings demonstrate the putative inhibitory role of sema3A in human neuroma tissue. Our observations are the first demonstration of the expression of sema3A in human neural scar tissue and support a role for this protein in the inhibition of axonal regeneration in injured human peripheral nerves. These findings contribute to the understanding of the outgrowth inhibitory properties of neuroma tissue.
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, An Institute of the Royal Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
authors.forename: Martijn R
authors.initials: MR
authors.lastname: Tannemaat
authors.forename: Joanna
authors.initials: J
authors.lastname: Korecka
authors.forename: Erich M E
authors.initials: EM
authors.lastname: Ehlert
authors.forename: Matthew R J
authors.initials: MR
authors.lastname: Mason
authors.forename: Sjoerd G
authors.initials: SG
authors.lastname: van Duinen
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Boer
authors.forename: Martijn J A
authors.initials: MJ
authors.lastname: Malessy
authors.forename: Joost
authors.initials: J
authors.lastname: Verhaagen
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D066298:In Vitro Techniques; D007223:Infant; D051379:Mice; D009412:Nerve Fibers / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000502:physiology*; D009463:Neuroma / Q000378:metabolism* / Q000473:pathology*; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D040121:Semaphorin-3A / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C108639:SEMA3A protein, human; D040121:Semaphorin-3A; D039942:Neuropilin-1