title: Investigation of sensory neurogenic components in a bleomycin-induced scleroderma model using transient receptor potential vanilloid 1 receptor- and calcitonin gene-related peptide-knockout mice.
abstract: OBJECTIVE
  Along with their classic afferent function (nociception), capsaicin-sensitive transient receptor potential vanilloid 1 (TRPV1) receptor-expressing sensory nerve terminals exert local and systemic efferent activities. Activation of TRPV1 causes sensory neuropeptide release, which modulates the inflammation process. The aim of the present study was to examine the role of this modulatory role of TRPV1 receptor and that of calcitonin gene-related peptide (CGRP) in bleomycin-induced scleroderma, using transgenic mice.
  
  
  METHODS
  Cutaneous sclerosis was induced with daily subcutaneous injections of bleomycin for 30 days. Control groups were treated with phosphate buffered saline (PBS). TRPV1 receptor gene-deficient (TRPV1(-/-)) mice and CGRP-knockout (CGRP(-/-)) mice and their wild-type (WT) counterparts were investigated. A composite sclerosis score was calculated on the basis of thickening, leukocyte infiltration, and the amount/orientation of collagen bundles. Dermal thickness and the number of alpha-smooth muscle actin (alpha-SMA)-positive cells were also determined. The quantity of the collagen-specific amino acid hydroxyproline was measured by spectrophotometry.
  
  
  RESULTS
  Bleomycin treatment induced marked cutaneous thickening and fibrosis compared with that observed in control mice treated with PBS. The composite sclerosis score was 18% higher, dermal thickness was 19% higher, the number of alpha-SMA-positive cells was 47% higher, and the amount of hydroxyproline was 57% higher in TRPV1(-/-) mice than in their WT counterparts. Similarly, the composite sclerosis score was 47% higher, dermal thickness was 29% higher, the number of alpha-SMA-positive cells was 76% higher, and the amount of hydroxyproline was 30% higher in CGRP(-/-) mice than in the respective WT groups.
  
  
  CONCLUSIONS
  These results suggest that activation of the TRPV1 receptor by mediators of inflammation induces sensory neuropeptide release, which might exert protective action against fibrosis. We confirmed the protective role of CGRP in the development of cutaneous sclerosis.
authors.affiliation: University of Pécs, Pécs, Hungary.
authors.forename: Arpád
authors.initials: A
authors.lastname: Szabó
authors.forename: László
authors.initials: L
authors.lastname: Czirják
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Sándor
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
authors.forename: Terézia
authors.initials: T
authors.lastname: László
authors.forename: Krisztián
authors.initials: K
authors.lastname: Elekes
authors.forename: Tamás
authors.initials: T
authors.lastname: Czömpöly
authors.forename: Anna
authors.initials: A
authors.lastname: Starr
authors.forename: Susan
authors.initials: S
authors.lastname: Brain
authors.forename: János
authors.initials: J
authors.lastname: Szolcsányi
authors.forename: Erika
authors.initials: E
authors.lastname: Pintér
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics*; D024042:Collagen Type I / Q000235:genetics; D020405:Dermis / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012595:Scleroderma, Systemic / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D050916:TRPV Cation Channels / Q000235:genetics*
chemical_list: D000903:Antibiotics, Antineoplastic; D024042:Collagen Type I; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D001761:Bleomycin; D015740:Calcitonin Gene-Related Peptide