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

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Presentation transcript:

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 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 Colocalizes to elastic fibres that ensure ECM integrity and elasticity Abundant in heart, lung, skin etc. Wulf-Johansson et al, 2013

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)

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

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

MFAP4 levels are changed in asthma WT OVA WT PBS

MFAP4 deficiency attenuates eosinophilic infiltration

Eosinophil chemoattractants are downregulated in MFAP4-deficient mice

Lack of MFAP4 attenuates mucus production PBS KO OVA WT OVA

MFAP4 contributes to asthmatic smooth muscle deposition

MFAP4 deficiency partially protects from AHR

Conclusions MFAP4 is increased in circulation and BAL of asthmatic mice. MFAP4 contributes to development of experimental asthma by: 1.Attraction of eosinophils through CCL11/CCL24 2.Goblet cell metaplasia 3.Smooth muscle deposition 4.AHR It suggests that MFAP4 can be a potential therapeutic target for allergic asthma.

Acknowledgements