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Role of YKL-40 in bronchial smooth muscle remodeling in asthma.

Abstract：

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.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Bara I,Ozier A,Girodet PO,Carvalho G,Cattiaux J,Begueret H,Thumerel M,Ousova O,Kolbeck R,Coyle AJ,Woods J,Tunon de Lara JM,Marthan R,Berger P

doi

10.1164/rccm.201105-0915OC

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

715-22

issue

eissn

1073-449X

issn

1535-4970

pii

rccm.201105-0915OC

journal_volume

185

pub_type

杂志文章

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Role of YKL-40 in bronchial smooth muscle remodeling in asthma.