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The role of microfibrillar-associated protein 4 (MFAP4) in asthma

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

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  1. The role of microfibrillar-associated protein 4 (MFAP4) in asthma Bartosz Pilecki PhD student Institute of Molecular Medicine University of Southern Denmark, Odense

  2. 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

  3. 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

  4. Hypothesis: • MFAP4 contributes to asthmatic airway disease, mainly due to its interaction with airway smooth muscle cells

  5. 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.

  6. MFAP4 levels are increased in asthma WT PBS WT OVA

  7. MFAP4 deficiency attenuates eosinophilic infiltration

  8. Eosinophil chemoattractants are downregulated in MFAP4-deficient mice

  9. Lack of MFAP4 attenuates mucus production PBS WT OVA KO OVA

  10. MFAP4 contributes to asthmatic smooth muscle deposition

  11. MFAP4 deficiency partially protects from AHR

  12. 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.

  13. Acknowledgements Christopher Stevenson, Novartis, UK Jorgen Vestbo, OUH, DK Niels Marcussen, OUH, DK Fonden til laegevidenskabens fremme

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