title: Undifferentiated bronchial fibroblasts derived from asthmatic patients display higher elastic modulus than their non-asthmatic counterparts.
abstract: During asthma development, differentiation of epithelial cells and fibroblasts towards the contractile phenotype is associated with bronchial wall remodeling and airway constriction. Pathological fibroblast-to-myofibroblast transition (FMT) can be triggered by local inflammation of bronchial walls. Recently, we have demonstrated that human bronchial fibroblasts (HBFs) derived from asthmatic patients display some inherent features which facilitate their FMT in vitro. In spite of intensive research efforts, these properties remain unknown. Importantly, the role of undifferentiated HBFs in the asthmatic process was systematically omitted. Specifically, biomechanical properties of undifferentiated HBFs have not been considered in either FMT or airway remodeling in vivo. Here, we combine atomic force spectroscopy with fluorescence microscopy to compare mechanical properties and actin cytoskeleton architecture of HBFs derived from asthmatic patients and non-asthmatic donors. Our results demonstrate that asthmatic HBFs form thick and aligned 'ventral' stress fibers accompanied by enlarged focal adhesions. The differences in cytoskeleton architecture between asthmatic and non-asthmatic cells correlate with higher elastic modulus of asthmatic HBFs and their increased predilection to TGF-β-induced FMT. Due to the obvious links between cytoskeleton architecture and mechanical equilibrium, our observations indicate that HBFs derived from asthmatic bronchi can develop considerably higher static tension than non-asthmatic HBFs. This previously unexplored property of asthmatic HBFs may be potentially important for their myofibroblastic differentiation and bronchial wall remodeling during asthma development.
authors: Department of Medical Physics and Biophysics, Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, Krakow, Poland.
authors: Michal
authors: M
authors: Sarna
authors: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland; Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors: Katarzyna A
authors: KA
authors: Wojcik
authors: Department of Plant Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors: Pawel
authors: P
authors: Hermanowicz
authors: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors: Dawid
authors: D
authors: Wnuk
authors: Department of Medical Physics and Biophysics, Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, Krakow, Poland.
authors: Kvetoslava
authors: K
authors: Burda
authors: Laboratory of Molecular Biology and Clinical Genetics, Medical College, Jagiellonian University, Krakow, Poland.
authors: Marek
authors: M
authors: Sanak
authors: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors: Jarosław
authors: J
authors: Czyż
authors: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors: Marta
authors: M
authors: Michalik
mesh_terms: D000328:Adult; D000368:Aged; D056151:Airway Remodeling / Q000187:drug effects; D001249:Asthma / Q000473:pathology*; D001980:Bronchi / Q000166:cytology* / Q000473:pathology*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects; D055119:Elastic Modulus / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000473:pathology*; D022001:Focal Adhesions / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000187:drug effects / Q000473:pathology; D022502:Stress Fibers / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D053773:Transforming Growth Factor beta1