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Published ahead of print on June 15, 2007, doi:10.1165/rcmb.2007-0089OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 37, pp. 424-430, 2007
© 2007 American Thoracic Society
DOI: 10.1165/rcmb.2007-0089OC

Cultured Lung Fibroblasts from Ovalbumin-Challenged "Asthmatic" Mice Differ Functionally from Normal

Hisatoshi Sugiura1, Xiangde Liu2, Fenghai Duan3, Shin Kawasaki2, Shinsaku Togo2, Koichiro Kamio2, Xing Qi Wang2, Lijun Mao4, Youngsoo Ahn2, Ronald F. Ertl2, Tom W. Bargar5, Abdo Berro6, Thomas B. Casale6 and Stephen I. Rennard2

1 Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan; 2 Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, Nebraska; 3 Preventive and Societal Medicine, University of Nebraska Medical Center, Omaha, Nebraska; 4 Department of Rheumatology, The Third Hospital of Peking University, Beijing, China; 5 Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska; and 6 Division of Allergy and Immunology, Creighton University Medical Center, Omaha, Nebraska

Correspondence and requests for reprints should be addressed to Stephen I. Rennard, M.D., University of Nebraska Medical Center, 985885 Nebraska Medical Center, Omaha, NE 68198-5885. E-mail: srennard{at}unmc.edu

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-beta1 (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-beta1 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.

Key Words: remodeling • fibroblast • phenotype • mouse model


CLINICAL RELEVANCE

Lung fibroblasts cultured from ovalbumin-sensitized mice manifest persistent differences in vitro in phenotypes related to repair and remodeling. This suggests that acquired alterations of fibroblast repair phenotypes can contribute to the pathogenesis of asthma.

 



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