Sensory neurons accelerate skin reepithelialization via substance P in an innervated tissue-engineered wound healing model.
Keratinocytes are responsible for reepithelialization and restoration of the epidermal barrier during wound healing. The influence of sensory neurons on this mechanism is not fully understood. We tested whether sensory neurons influence wound closure via the secretion of the neuropeptide substance P (SP) with a new tissue-engineered wound healing model made of an upper-perforated epidermal compartment reconstructed with human keratinocytes expressing green fluorescent protein, stacked over a dermal compartment, innervated or not with sensory neurons. We showed that sensory neurons secreted SP in the construct and induced a two times faster wound closure in vitro. This effect was partially reproduced by addition of SP in the model without neurons, and completely blocked by a treatment with a specific antagonist of the SP receptor neurokinin-1 expressed by keratinocytes. However, this antagonist did not compromise wound closure compared with the control. Similar results were obtained when the model with or without neurons was transplanted on CD1 mice, while wound closure occurred faster. We conclude that sensory neurons play an important, but not essential, role in wound healing, even in absence of the immune system. This model is promising to study the influence of the nervous system on reepithelialization in normal and pathological conditions.
1 Centre LOEX de l'Université Laval , Centre de recherche du CHU de Québec, Québec, Canada .
Mathieu
M
Blais
Lorène
L
Mottier
Marie-Anne
MA
Germain
Sabrina
S
Bellenfant
Sébastien
S
Cadau
François
F
Berthod
D016475:3T3 Cells; D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects / Q000254:growth & development; D004848:Epithelium / Q000187:drug effects / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008954:Models, Biological; D009412:Nerve Fibers / Q000187:drug effects; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000294:innervation* / Q000473:pathology*; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D023822:Tissue Engineering / Q000379:methods*; D014945:Wound Healing / Q000187:drug effects
D009479:Neuropeptides; C065446:spantide II; D013373:Substance P