Document Detail

Role of YKL-40 in bronchial smooth muscle remodeling in asthma.
MedLine Citation:
PMID:  22281830     Owner:  NLM     Status:  MEDLINE    
RATIONALE: 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.
OBJECTIVES: 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.
MEASUREMENTS AND MAIN 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.
Imane Bara; Annaig Ozier; Pierre-Olivier Girodet; Gabrielle Carvalho; Jennifer Cattiaux; Hugues Begueret; Matthieu Thumerel; Olga Ousova; Roland Kolbeck; Anthony J Coyle; Joanne Woods; Jose-Manuel Tunon de Lara; Roger Marthan; Patrick Berger
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-26
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  185     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-02     Completed Date:  2012-05-16     Revised Date:  2012-10-12    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  715-22     Citation Subset:  AIM; IM    
Université Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux, France.
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MeSH Terms
Adipokines / blood,  physiology*
Airway Remodeling / physiology*
Apoptosis / physiology
Asthma / blood,  physiopathology*
Blotting, Western
Bronchi / cytology,  physiopathology*
Cell Count
Cell Movement / physiology
Cell Proliferation
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Lectins / blood,  physiology*
Middle Aged
Muscle, Smooth / cytology,  physiopathology*
Receptor, PAR-2 / physiology
Signal Transduction / physiology
Young Adult
Reg. No./Substance:
0/Adipokines; 0/CHI3L1 protein, human; 0/Lectins; 0/Receptor, PAR-2
Comment In:
Am J Respir Crit Care Med. 2012 Apr 1;185(7):692-4   [PMID:  22467800 ]
Am J Respir Crit Care Med. 2012 Aug 15;186(4):386; author reply 386-7   [PMID:  22896594 ]

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