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The role of microfibrillar-associated protein 4 (MFAP4) in asthma. Bartosz Pilecki PhD student Institute of Molecular Medicine University of Southern Denmark, Odense. Asthma. Common chronic airway disease
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The role of microfibrillar-associated protein 4 (MFAP4) in asthma Bartosz Pilecki PhD student Institute of Molecular Medicine University of Southern Denmark, Odense
Asthma • Common chronic airway disease • Decrease in lung function due to persistent inflammation, airway remodeling and airway hyperresponsiveness (AHR) • Current treatments effective only in selected subsets of patients
MFAP4 • Extracellular matrix (ECM) protein that binds to elastin and collagen • Abundant in heart, lung, skin etc. • Promotes proliferation and migration of vascular SMC in an integrin-dependent manner (Schlosser et al, submitted) Wulf-Johansson et al, 2013
Hypothesis: • MFAP4 contributes to asthmatic airway disease, mainly due to its interaction with airway smooth muscle cells
In vivo allergy models • OVA model: • House dust mite (HDM) chronic model: Day: 0-4 5-6 rest 7 weeks 25 ug HDM i.n.
MFAP4 levels are increased in asthma WT PBS WT OVA
Eosinophil chemoattractants are downregulated in MFAP4-deficient mice
Lack of MFAP4 attenuates mucus production PBS WT OVA KO OVA
Conclusions MFAP4 isincreasedincirculation and BAL of asthmatic mice. MFAP4 contributes to development of experimental asthma by: • Attraction of eosinophilsthrough CCL11/CCL24 • Goblet cell metaplasia • Smooth muscle deposition • AHR • Itsuggeststhat MFAP4 can be a potentialtherapeutic target for allergicasthma.
Acknowledgements Christopher Stevenson, Novartis, UK Jorgen Vestbo, OUH, DK Niels Marcussen, OUH, DK Fonden til laegevidenskabens fremme