Bronchial epithelial compression regulates epidermal growth factor receptor family ligand expression in an autocrine manner
ABSTRACT The epidermal growth factor receptor (EGFR), an important signaling pathway in airway biology, is stimulated by compressive stress applied to human airway epithelial cells. Although the EGFR ligand, heparin-binding epidermal growth factor-like growth factor (HB-EGF), is known to be released as a result of this stimulation, whether compressive stress enhances expression of other EGFR ligands, and the duration of mechanical compression required to initiate this response, is not known. Human airway epithelial cells were exposed to compressive stress, and expression of four EGFR ligands was examined by quantitative PCR. Cells were exposed to: (1) continuous compressive stress over 8 h, (2) compression with and without EGFR inhibitor (AG1478), or (3) time-limited compression (3.75, 7.5, 15, 30, and 60 min). Compressive stress produced a sustained upregulation of the EGFR ligands HB-EGF, epiregulin, and amphiregulin, but not transforming growth factor-alpha. Inhibition with AG1478 demonstrated that expression of HB-EGF, epiregulin, and amphiregulin is dependent on the signaling via the EGFR. Immunostaining for epiregulin protein demonstrated increased expression with compression and attenuation with EGFR inhibition. The response of all three EGFR ligands persisted long after the mechanical stimulus was removed. Taken together, these data suggest the possibility of a mechanically activated EGFR autocrine feedback loop involving selected EGFR ligands.
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- "A similar hypertrophic effect can be seen in arteries as a result of hypertension (high blood pressure) . Other tissues where development is affected by mechanical loading are cartilage , the airway  , and the endothelial lining of blood vessels . "
ABSTRACT: The biomechanical modeling of growing tissues has recently become an area of intense interest. In particular, the interplay between growth patterns and mechanical stress is of great importance, with possible applications to arterial mechanics, embryo morphogenesis, tumor development, and bone remodeling. This review aims to give an overview of the theories that have been used to model these phenomena, categorized according to whether the tissue is considered as a continuum object or a collection of cells. Among the continuum models discussed is the deformation gradient decomposition method, which allows a residual stress field to develop from an incompatible growth field. The cell-based models are further subdivided into cellular automata, center-dynamics, and vertex-dynamics models. Of these the second two are considered in more detail, especially with regard to their treatment of cell–cell interactions and cell division. The review concludes by assessing the prospects for reconciliation between these two fundamentally different approaches to tissue growth, and by identifying possible avenues for further research.SIAM Review 01/2012; 54(1):52-118. DOI:10.1137/080731785 · 4.79 Impact Factor
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ABSTRACT: Airway wall remodeling is a hallmark of asthma, characterized by subepithelial thickening and extracellular matrix (ECM) remodeling. Mechanical stress due to hyperresponsive smooth muscle cells may contribute to this remodeling, but its extent and relevance in a 3D environment (where the ECM plays an important role in modulating stresses felt by cells) are unclear. To characterize the effects of dynamic compression in ECM remodeling in a physiologically relevant 3D tissue model of the human airway wall, a tissue engineered human airway wall model with differentiated bronchial epithelial cells atop a collagen gel containing lung fibroblasts was developed. Lateral compressive strain of 10% or 30% at 1 or 60 cycles per hour was applied using a novel straining device. ECM remodeling was assessed by immunohistochemistry and zymography. Dynamic strain, particularly at the lower magnitude, induced airway wall remodeling as indicated by increased deposition of types III and IV collagen and increased secretion of matrix metalloproteinase-2 and -9. These changes paralleled increased myofibroblast differentiation. Furthermore, the spatial pattern of type III collagen deposition correlated with that of myofibroblasts; both were concentrated near the epithelium and decreased diffusely away from the surface, indicating some epithelial control of the remodeling response. Thus, in a physiologically relevant 3D model of the bronchial wall, dynamic compressive strain induced tissue remodeling that mimics many features of remodeling seen in asthma, in the absence of inflammation
Conference Paper: The Design and Modelling of Automated Broadband Slide-Screw Tuners[Show abstract] [Hide abstract]
ABSTRACT: This paper reviews the most recent automated tuning techniques and comments on their respective advantages. The development of a simple model, capable of predicting the response of a slide-screw tuner from 45 MHz to 18 GHz, is described and compared with measurements of an existing tuner. The parameters affecting slide-screw tuner performance are identified with particular attention being paid to the slug. A tuning slug design is presented achieving optimum tuner performance over the 2 to 18 GHz frequency range.ARFTG Conference Digest-Spring, 29th; 07/1987