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23 June 2009

Asthmatic bronchial fibroblasts demonstrate enhanced potential to differentiate into myofibroblasts in culture

Marta MichalikABCDEFG, Malgorzata PierzchalskaBCDEFG, Agnieszka LegutkoABC, Marcin UraB, Anna OstaszewskaB, Jerzy SojaB, Marek SanakG

Med Sci Monit 2009; 15(7): BR194-201 :: ID: 869704

Abstract

Background
Chronic inflammation and remodeling of the bronchial wall are basic hallmarks of asthma. It is known that mesenchymal cells in the lamina reticularis underlying the basement membrane of the thickened airway wall of asthmatics predominantly display the phenotype of myofibroblasts and express alpha-smooth muscle actin (alpha-SMA). Human bronchial fibroblasts (HBFs) transform in vitro into myofibroblasts under the influence of transforming growth factor (TGF-beta). Differences in the reactivity of fibroblasts to TGF-beta in cultures derived from healthy and asthmatic donors are elucidated here.
Material and Method
Primary human bronchial fibroblasts (HBFs) were cultured from bronchial biopsies from non-asthmatic (n=7) and asthmatic (n=7) donors and treated with TGF-beta1 or TGF-beta2 to induce myofibroblast differentiation. Expression of alpha-smooth muscle actin (alpha-SMA) was assessed by immunocytochemistry and Western blotting. The cell size and shape parameters were measured by computer-aided methods.
Results
Regardless of whether TGF-beta1 or TGF-beta2 was used, asthmatic cells showed enhanced expression of the myofibroblast marker as confirmed by immunocytochemistry and immunoblotting. Analysis of the shape parameters of cells incubated in the presence of TGF-beta1 revealed that HBFs of asthmatics differ from those of non-asthmatics.
Conclusions
It is concluded that asthmatic HBFs cultured in vitro display some inherent features which facilitate their differentiation into myofibroblasts. These data indicate that increased reactivity of asthmatic fibroblasts to TGF-beta may play a crucial role in asthma.

Keywords: Fibroblasts - drug effects, Cells, Cultured, Cell Size - drug effects, Cell Shape - drug effects, Cell Differentiation - drug effects, Asthma - pathology, Actins - metabolism, Transforming Growth Factor beta1 - pharmacology

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750