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This project will evaluate the effect of chronic exposure to house dust mite (HDM) on the bronchial smooth muscle (BSM) remodelling observed in asthma and particularly the number of mitochondria. Indeed, the increased number of mitochondria is a key factor of BSM remodelling. The increased mass of BSM in asthma is still insensitive to current therapeutics, and has been associated with a poor prognosis including decrease in lung function and high morbidity. In addition, chronic exposure to HDM is an important determinant of asthma control but preventing human exposure to HDM allergens is difficult to implement. Thus, a better understanding of the effect of chronic exposure to BSM remodelling and reversing BSM remodelling must be the main objectives for the future treatment of asthma. The general aim of this project is to determine the effect of HDM on BSM mitochondria. The specific aims are (i) to determine the effects of chronic exposure to HDM on BSM mitochondria in vivo, (ii) to explore the effects of chronic exposure to HDM on BSM mitochondria in an in vitro model of BE/BSM interaction, (iii) to identify the role of mitochondria in allergic asthmatic BSM cell apoptosis in vitro, and (iv) to develop pro-apoptotic strategies of allergic asthmatic BSM cells targeted on mitochondria. This is a translational project which associates in vivo approach using a murine model of asthma, and in vitro approaches using BSM cells obtained from allergic asthmatic patients. For this purpose, we will use samples from recent clinical trials such as “Remodel’Asthme” study supported by both PHRC and INSERM-DHOS grants.
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