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PhD defence T. Koopmans

When:Fr 20-10-2017 at 12:45
Where:Academy Building

WNT and β-catenin signalling in airway smooth muscle: emerging concepts for asthma

Asthma is a common disease of the airways characterised by chronic inflammation. Symptoms are recurring, and result in obstruction of the airways and bronchospasm. The airway smooth muscle is principally involved in airway obstruction, through contraction, non-reversible thickening, or production of inflammatory compounds. When referring to the smooth muscle, current therapies for asthma focus primarily on bronchodilatation, while no specific treatment strategy exists for the remaining features of asthma, among which increased muscle thickness.

Tim Koopmans describes in his thesis the role of so-called WNT growth factors in these events. "We show that WNT growth factors in several ways contribute to the pathophysiology of asthma. These conclusions were drawn from the use of airway smooth muscle cells that were cultured, but also through transgenic mice that overproduce WNT growth factors in the muscle. From these models we have learned that the factor WNT-5A, whose expression is elevated in the muscle of asthmatics, promotes contractility of the muscle, but is also released by the cell to increase inflammatory interactions with neighbouring inflammatory cells. WNT growth factors are also involved with thickening of the muscle. In allergen-exposed mice who received a pharmacological compound that inhibits this pathway, we observed a drastic reduction in smooth muscle thickness.

This research shows that WNT growth factors, especially WNT-5A, can contribute to the chronic pathology of allergic asthma. Pharmacological inhibition of WNT growth factors may potentially dilate the airways as well as inhibit inflammation, and even reduce muscle thickness. Through our findings we have obtained new insight into possible future therapies aimed at the chronic component of asthma, including muscle thickness, for which to date no pharmacological treatment exists."

Dissertation

Promotores: Prof.dr. R. Gosens en Prof.dr. H. Meurs

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