Abstract
BackgroundMechanical strain alters protein expression. It results in phosphorylation of MAP kinases and up-regulation of extracellular matrix proteins. We investigated whether phosphorylation of MAP kinase family members was increased in response to mechanical strain in fibroblasts from asthmatic patients (AF) and normal controls (NF), and whether phosphorylation of these signaling molecules would be different in the two cell populations.MethodsFibroblasts were obtained from mild, atopic asthmatics and non-atopic volunteers using endobronchial biopsy. Cells were grown on flexible, collagen I-coated membranes, and subjected to mechanical strain (Flexercell). MAP kinase phosphorylation was measured at baseline, and during one hour of strain. We also examined the effect of strain on proteoglycan production.ResultsAt baseline, there was increased phosphorylation of ERK1/2 and p38, and decreased phosphorylation of JNK in AF vs NF. During strain in NF, p38 phosphorylation was increased. Conversely in AF, strain resulted in an increase in JNK phosphorylation, had no effect on phosphorylation of p38, and resulted in a decrease in ERK1/2 phosphorylation. There was a significant increase in versican protein production after 24 h strain in both AF and NF. JNK inhibition reversed the strain-induced increase in versican in NF, but had no effect in AF.ConclusionThese results show that there are phenotypic differences in MAP kinase phosphorylation in AF vs NF, and that different signaling pathways are involved in transducing mechanical stimuli in these two populations of cells.
Highlights
Mechanical strain affects the production of extracellular matrix (ECM) components, upregulating type I collagen in pulmonary fibroblasts, type III and IV collagen in co-cultures of bronchial epithelial cells and lung fibroblasts, and the proteoglycans (PGs), versican, biglycan and perlecan, in human arterial smooth muscle cells [7,8,9]
mitogen-activated protein (MAP) kinase activation is increased in asthmatic fibroblasts (AF) vs NF At baseline, the phosphorylation of ERK1/2 was increased 1.65 fold in AF in comparison to NF (Figure 1A, p < 0.05)
Mechanical strain resulted in differential phosphorylation of MAP kinases in AF vs NF In NF, there was a trend to increased ERK1/2 phosphorylation with a maximum occurring at 20 min of strain (Figure 2A)
Summary
It results in phosphorylation of MAP kinases and up-regulation of extracellular matrix proteins. We investigated whether phosphorylation of MAP kinase family members was increased in response to mechanical strain in fibroblasts from asthmatic patients (AF) and normal controls (NF), and whether phosphorylation of these signaling molecules would be different in the two cell populations. Phosphorylation of c-Jun NH2-terminal kinase (JNK) is increased in response to mechanical strain in both bronchial epithelial cells and in type II-like alveolar epithelial cells [3,6]. Mechanical strain affects the production of extracellular matrix (ECM) components, upregulating type I collagen in pulmonary fibroblasts, type III and IV collagen in co-cultures of bronchial epithelial cells and lung fibroblasts, and the proteoglycans (PGs), versican, biglycan and perlecan, in human arterial smooth muscle cells [7,8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
