Cultured lung fibroblasts from ovalbumin-challenged "asthmatic" mice differ functionally from normal.
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.
Sugiura
Hisatoshi
H
Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
Liu
Xiangde
X
Duan
Fenghai
F
Kawasaki
Shin
S
Togo
Shinsaku
S
Kamio
Koichiro
K
Wang
Xing Qi
XQ
Mao
Lijun
L
Ahn
Youngsoo
Y
Ertl
Ronald F
RF
Bargar
Tom W
TW
Berro
Abdo
A
Casale
Thomas B
TB
Rennard
Stephen I
SI
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
D000199:Actins; D005353:Fibronectins; D005782:Gels; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D010047:Ovalbumin; D003094:Collagen