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Research Report 1 : Mechanisms involved in the induction of airway remodeling due to bronchoconstriction

Muis, J. (2013) Research Report 1 : Mechanisms involved in the induction of airway remodeling due to bronchoconstriction. Master's Thesis / Essay, Biology.

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Chronic airway diseases, like asthma or COPD, are characterized by hyperresponsiveness resulting in inflammation and bronchoconstriction. During these diseases, also remodeling of the airway tissue occurs. Smooth muscle hypertrophy, epithelial goblet-cell hyperplasia and collagen deposition are examples of airway remodeling. Recent findings suggest a role for muscarinic receptor stimulation regulating remodeling in chronic airway diseases. Besides, other recently published data suggest that mechanical stress caused by bronchoconstriction may cause remodeling independent of inflammation. In this study, methacholine was used to induce bronchoconstriction, but methacholine is also a muscarinic agonist. Mainly due to this last article, the question arose which mechanisms are involved in the induction of airway remodeling by bronchoconstriction. That is why we designed a model to examine if the effect of methacholine is attributable to cell signaling or to the mechanical forces caused by bronchocon striction. We used isometric and isotonic contraction experiments to induce mechanical strain in bovine airway smooth muscle strips and added methacholine to induce both bronchoconstriction and cell signaling via muscarinic receptors. The strips were tested on several protein levels with western blot. Contractile protein levels in chronic stimulated strips did not show strain-dependent increases. The acute stimulated strips with isometric settings did show a significant increased phosphorylated ERK 1/2 and GSK-3 level at 10 grams of tension. In case of phosphorylated ERK 1/2, this increase is probably strain-dependent. Methacholine was able to further increase the levels, but not on a strain-dependent manner. Besides, we tested if the phosphorylation of ERK 1/2 was attributable to Rho kinase-induced contraction, but this was not demonstrated. However, we did see an inhibitory effect on the contractility of methacholine induced strips. With regard to this last point, more experiments are recommended to investigate this properly. The main aim of this study to design a model to investigate whether the increasing effect of methacholine on airway remodeling markers was due to cell signaling or to the mechanical forces caused by constriction of the trachea has not yet been achieved.

Item Type: Thesis (Master's Thesis / Essay)
Degree programme: Biology
Thesis type: Master's Thesis / Essay
Language: English
Date Deposited: 15 Feb 2018 07:54
Last Modified: 15 Feb 2018 07:54

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