Post on 21-Dec-2015
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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