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

Bartosz PileckiPhD student

Institute of Molecular MedicineUniversity 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

25 ug HDM i.n.

7 weeks

MFAP4 levels are increased 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 OVAWT OVA

MFAP4 contributes to asthmatic smooth muscle deposition

MFAP4 deficiency partially protects from AHR

ConclusionsMFAP4 is increased in circulation and BAL of asthmatic mice.

MFAP4 contributes to development of experimental asthma by:1. Attraction of eosinophils through CCL11/CCL242. Goblet cell metaplasia3. Smooth muscle deposition4. AHR

It suggests that MFAP4 can be a potential therapeutic target for allergic asthma.

AcknowledgementsChristopher Stevenson,

Novartis, UK

Jorgen Vestbo, OUH, DKNiels Marcussen, OUH, DK

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