title: Cultured lung fibroblasts from ovalbumin-challenged "asthmatic" mice differ functionally from normal.
abstract: Asthmatic airway remodeling is characterized by goblet cell hyperplasia, angiogenesis, smooth muscle hypertrophy, and subepithelial fibrosis. This study evaluated whether acquired changes in fibroblast phenotype could contribute to this remodeling. Airway and parenchymal fibroblasts from control or chronically ovalbumin (OVA)-sensitized and challenged "asthmatic" mice were assessed for several functions related to repair and remodeling +/- exogenous transforming growth factor (TGF)-beta. All OVA-challenged mouse fibroblasts demonstrated augmented gel contraction (P < 0.05) and chemotaxis (P < 0.05); increased TGF-beta(1) (P < 0.05), fibronectin (P < 0.05), and vascular endothelial growth factor (P < 0.05) release; and expressed more alpha-smooth muscle actin (P < 0.05). TGF-beta(1) stimulated both control and asthmatic fibroblasts, which retained all differences from control fibroblasts for all features(P < 0.05, all comparisons). Parenchymal fibroblasts proliferated more rapidly (P < 0.05), while airway fibroblasts proliferated similarly compared with control fibroblasts (P = 0.25). Thus, in this animal model, OVA-challenged mouse fibroblasts acquire a distinct phenotype that differs from control fibroblasts. The augmented profibrotic activity and mediator release of asthmatic fibroblasts could contribute to airway remodeling in asthma.
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Sugiura
authors.forename: Xiangde
authors.initials: X
authors.lastname: Liu
authors.forename: Fenghai
authors.initials: F
authors.lastname: Duan
authors.forename: Shin
authors.initials: S
authors.lastname: Kawasaki
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Togo
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kamio
authors.forename: Xing Qi
authors.initials: XQ
authors.lastname: Wang
authors.forename: Lijun
authors.initials: L
authors.lastname: Mao
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Ahn
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Ertl
authors.forename: Tom W
authors.initials: TW
authors.lastname: Bargar
authors.forename: Abdo
authors.initials: A
authors.lastname: Berro
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Casale
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000473:pathology*; D001985:Bronchial Provocation Tests; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005353:Fibronectins / Q000378:metabolism; D005782:Gels; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000494:pharmacology*; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000199:Actins; D005353:Fibronectins; D005782:Gels; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D010047:Ovalbumin; D003094:Collagen