title: Role of neurotrophins on dermal fibroblast survival and differentiation.
abstract: Neurotrophins (NTs) belong to a family of growth factors that play a critical role in the control of skin homeostasis. NTs act through the low-affinity receptor p75NTR and the high-affinity receptors TrkA, TrkB, and TrkC. Here we show that dermal fibroblasts (DF) and myofibroblasts (DM) synthesize and secrete all NTs and express NT receptors. NTs induce differentiation of DF into DM, as shown by the expression of α-SMA protein. The Trk inhibitor K252a, TrkA/Fc, TrkB/Fc, or TrkC/Fc chimera prevents DF and DM proliferation. In addition, p75NTR siRNA inhibits DF proliferation, indicating that both NT receptors mediate DF proliferation induced by endogenous NTs. Autocrine NTs also induce DF migration through p75NTR and Trk, as either silencing of p75NTR or Trk/Fc chimeras prevent this effect, in absence of exogenous NTs. Finally, NGF or BDNF statistically increase the tensile strength in a dose dependent manner, as measured in a collagen gel through the GlaSbox device. Taken together, these results indicate that NTs exert a critical role on fibroblast and could be involved in tissue re-modeling and wound healing.
authors.affiliation: Institute of Dermatology, School of Biosciences and Biotechnologies, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Palazzo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marconi
authors.forename: Francesca
authors.initials: F
authors.lastname: Truzzi
authors.forename: Katiuscia
authors.initials: K
authors.lastname: Dallaglio
authors.forename: Tiziana
authors.initials: T
authors.lastname: Petrachi
authors.forename: Philippe
authors.initials: P
authors.lastname: Humbert
authors.forename: Sylvianne
authors.initials: S
authors.lastname: Schnebert
authors.forename: Eric
authors.initials: E
authors.lastname: Perrier
authors.forename: Marc
authors.initials: M
authors.lastname: Dumas
authors.forename: Carlo
authors.initials: C
authors.lastname: Pincelli
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D052816:Foreskin; D048091:Guided Tissue Regeneration / Q000379:methods; D006801:Humans; D008297:Male; D058628:Myofibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism / Q000502:physiology*; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000502:physiology*; D020917:Receptor, trkA / Q000235:genetics / Q000502:physiology; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014945:Wound Healing / Q000235:genetics / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC