title: Modulatory role of sensory innervation on hair follicle stem cell progeny during wound healing of the rat skin.
abstract: BACKGROUND
  The bulge region of the hair follicle contains resident epithelial stem cells (SCs) that are activated and mobilized during hair growth and after epidermal wounding. However, little is known about the signals that modulate these processes. Clinical and experimental observations show that a reduced supply of sensory innervation is associated with delayed wound healing. Since axon terminals of sensory neurons are among the components of the bulge SC niche, we investigated whether these neurons are involved in the activation and mobilization of the hair stem cells during wound healing.
  
  
  RESULTS
  We used neonatal capsaicin treatment to reduce sensory terminals in the rat skin and performed morphometric analyses using design-based stereological methods. Epithelial proliferation was analyzed by quantifying the number of bromodeoxyuridine-labeled (BrdU(+)) nuclei in the epidermis and hair follicles. After wounding, the epidermis of capsaicin-treated rats presented fewer BrdU(+) nuclei than in control rats. To assess SC progeny migration, we employed a double labeling protocol with iododeoxyuridine and chlorodeoxyuridine (IdU(+)/CldU(+)). The proportion of double-labeled cells was similar in the hair follicles of both groups at 32 h postwounding. IdU(+)/CldU(+) cell proportion increased in the epidermis of control rats and decreased in treated rats at 61 h postwounding. The epidermal volume immunostained for keratin 6 was greater in treated rats at 61 h. Confocal microscopy analysis revealed that substance P (SP) and calcitonin gene-related peptide (CGRP) receptor immunoreactivity were both present in CD34(+) and BrdU-retaining cells of the hair follicles.
  
  
  CONCLUSIONS
  Our results suggest that capsaicin denervation impairs SC progeny egress from the hair follicles, a circumstance associated with a greater epidermal activation. Altogether, these phenomena would explain the longer times for healing in denervated skin. Thus, sensory innervation may play a functional role in the modulation of hair SC physiology during wound healing.
authors.affiliation: Departamento de Biología Celular y Fisiología and Grupo Multidisciplinario de Investigación en Células Troncales IMPULSA 02, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Coyoacán, Distrito Federal, México. emartin@biomedicas.unam.mx
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martínez-Martínez
authors.forename: Claudio I
authors.initials: CI
authors.lastname: Galván-Hernández
authors.forename: Brenda
authors.initials: B
authors.lastname: Toscano-Márquez
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gutiérrez-Ospina
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003714:Denervation; D018859:Hair Follicle / Q000187:drug effects / Q000294:innervation* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018013:Receptors, Neuropeptide / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000473:pathology*; D055153:Stem Cell Niche / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D018013:Receptors, Neuropeptide; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin