title: Role of YKL-40 in bronchial smooth muscle remodeling in asthma.
abstract: BACKGROUND
  Bronchial remodeling, including increased bronchial smooth muscle (BSM) mass, contributes to bronchial obstruction in asthma. However, its mechanisms are complex and remain controversial. Recently, a role of the chitinase 3-like 1 protein (YKL-40) has been evoked in asthma. Indeed, YKL-40 concentration was increased in asthmatic serum, and correlated with asthma severity and subepithelial membrane thickness. Nevertheless, the role of YKL-40 on BSM cells remains to be investigated.
  
  
  OBJECTIVE
  To evaluate whether YKL-40 altered the physiologic properties of BSM cells in asthma in vitro and ex vivo.
  
  
  METHODS
  We enrolled 40 subjects with asthma, 13 nonsmokers, and 16 smokers. BSM cells were derived from bronchial specimens obtained by either fiberoptic bronchoscopy or lobectomy. We assessed cell proliferation using BrdU, flow cytometry, and cell count; signaling intermediates using Western blot; cell migration using inserts, wound healing, and phalloidin staining; and cell synthesis using ELISA and Western blot. The involvement of protease activated receptor (PAR)-2 was evaluated using blocking antibody and dedicated lentiviral small hairpin RNA. We also determined the BSM area and the YKL-40 staining ex vivo using immunohistochemistry on biopsies from subjects with asthma and control subjects.
  
  
  RESULTS
  We demonstrated that YKL-40 increased BSM cell proliferation and migration through PAR-2-, AKT-, ERK-, and p38-dependent mechanisms. The increased cell migration was higher in BSM cells of subjects with asthma than that of control subjects. Furthermore, YKL-40 epithelial expression was positively correlated with BSM mass in asthma.
  
  
  CONCLUSIONS
  This study indicates that YKL-40 promotes BSM cell proliferation and migration through a PAR-2-dependent mechanism.
authors.affiliation: Université Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux, France.
authors.forename: Imane
authors.initials: I
authors.lastname: Bara
authors.forename: Annaig
authors.initials: A
authors.lastname: Ozier
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Girodet
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Carvalho
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cattiaux
authors.forename: Hugues
authors.initials: H
authors.lastname: Begueret
authors.forename: Matthieu
authors.initials: M
authors.lastname: Thumerel
authors.forename: Olga
authors.initials: O
authors.lastname: Ousova
authors.forename: Roland
authors.initials: R
authors.lastname: Kolbeck
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: Joanne
authors.initials: J
authors.lastname: Woods
authors.forename: Jose-Manuel
authors.initials: JM
authors.lastname: Tunon de Lara
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.forename: Patrick
authors.initials: P
authors.lastname: Berger
mesh_terms: D054392:Adipokines / Q000097:blood / Q000502:physiology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D056151:Airway Remodeling / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology; D001249:Asthma / Q000097:blood / Q000503:physiopathology*; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000503:physiopathology*; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D000071451:Chitinase-3-Like Protein 1; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D037102:Lectins / Q000097:blood / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000166:cytology / Q000503:physiopathology*; D044464:Receptor, PAR-2 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D055815:Young Adult
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D044464:Receptor, PAR-2