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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 inflammatory airway disease Symptoms: airflow obstruction, shortness of breath

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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 inflammatory airway disease • Symptoms: airflow obstruction, shortness of breath • 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 • Colocalizes to elastic fibres that ensure ECM integrity and elasticity • Abundant in heart, lung, skin etc. Wulf-Johansson et al, 2013

  4. MFAP4 functions • The biological function of MFAP4 is not fully documented: • Contains Arg-Gly-Asp (RGD) sequence (integrin binding) • Promotes proliferation and migration of vascular SMC in an integrin-dependent manner (Schlosser et al, in preparation)

  5. Hypothesis: • MFAP4 contributes to asthma development or progression, mainly due to its interaction with airway smooth muscle cells through integrins

  6. In vivo allergy models • Acute OVA model: • House dust mite (HDM) chronic model: Day: 0-4 5-6 rest 7 weeks 25 ug HDM i.n.

  7. MFAP4 levels are changed in asthma WT PBS WT OVA

  8. MFAP4 deficiency attenuates eosinophilic infiltration

  9. Eosinophil chemoattractants are downregulated in MFAP4-deficient mice

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

  11. MFAP4 contributes to asthmatic smooth muscle deposition

  12. MFAP4 deficiency partially protects from AHR

  13. 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.

  14. Acknowledgements

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