Psoriasis

Understanding how mechanical stress contributes to psoriasis progression

Psoriatic plaques characteristically localize to knees and elbows, skin regions that are particularly subject to mechanical stress. Moreover, patients often develop plaques at sites of trauma (Koebner phenomenon). About one in four patients develop arthritis and trauma/mechanical load is thought to play a role in the pathogenesis of enthesitis and psoriatic arthritis.

Most cells in vivo, as well as in culture, respond to mechanical stress with increased cell proliferation. Intracellular changes in calcium concentrations, or “calcium signals” and activation of mitogen-activated protein (MAP) kinases have been shown to play key roles in mechanosignalling and regulation of proliferation. Interestingly, both pathways have been implicated in the development of psoriatic plaques.

The aim of the project is test the hypothesis that psoriatic keratinocytes are hyper-responsive to mechanical stress and that this hypersensitivity contributes to the development of psoriatic plaque following skin trauma.

In a collaborative project with the head of our department, Professor Nick Reynolds and our senior technician, Carole Todd, Dr. Anna Brown (postdoc, 10/09-02/12) demonstrated that p38 MAP kinase signalling upon mechanical stretch is altered in psoriatic keratinocytes (Brown et al., 42nd Annual Meeting of the European Society for Dermatological Research (ESDR). 2012 , Venice, Italy: Nature Publishing Group).

Work on this project is supported by the Psoriasis Association.