University Clinics in the Nordic Countries
Ingrid Asp Psoriasis Research Center
Charlotta Enerbäck
Ingrid Asp Psoriasis Research Center, Linköping University, SE-581 83 Linköping, Sweden. E-mail: charlotta. enerback @ liu. se
A generous donation to Linköping University made possible the establishment of the Ingrid Asp Foundation for Psoriasis Research to strengthen, broaden and deepen research into psoriasis. As a result, the Ingrid Asp Psoriasis Research Center was inaugurated in spring 2012. Since then, we have built a strong research platform devoted to psoriasis research. The research group includes Cecilia Bivik Eding and Deepti Verma( PhD, principal research engineers) and Gunna Sigurdardóttir and Ines Köhler( MD, dermatologists, PhD students). At the Division of Dermatology, we have a well-equipped laboratory for cell culture, biomedical analyses and molecular biology. The Medical Faculty at Linköping University provides core facilities, including advanced equipment and technical support for flow cytometry, molecular biology and microscopy. Animal studies are performed at the Center for Biomedical Research core facility.
Specific aims
Psoriasis is an immunologically-mediated inflammatory disease with strong genetic susceptibility. It is a painful, disabling condition that affects 2 – 3 % of the population of the Western world. The disease is characterized by distinctive skin eruptions showing intense hyperproliferation and disturbed maturation of the epidermal cells and an inflammatory dermal infiltrate, a combination of changes that is reminiscent of those seen in cancer. However, one important distinction is that the epithelial proliferation in psoriasis remains under very strict control. While much progress has been made in our understanding of the pathogenesis of psoriasis, many of the fundamental cellular activities that are crucial for the development of psoriasis are poorly understood. In fact, the role of keratinocytes( KCs) in the formation of the psoriatic lesion has received very limited attention. Furthermore, the genetic predisposition in psoriasis is well described, but there is an urgent need to clarify the biological consequences of the disease-associated genetic variants in order to better understand the pathophysiological mechanisms that drive the disease.
Our specific aims are as follows: Dermal lesion: To explore the equilibrium between proliferation, differentiation and apoptosis in the formation of psoriatic plaque and to evaluate experimentally whether increased apoptosis by MTH1 inhibitors may hamper this process.
The genetic and epigenetic predisposition: To investigate the mechanism by which genetic variants in susceptibility genes lead to psoriasis and to investigate whether epigenetic alterations contribute to the heredity and disease susceptibility in psoriasis.
Research areas Studies of the dermal lesion in psoriasis
We have previously focused our interest on psoriasin( S100A7), a calcium-binding protein of the S100 family, which was originally identified as being highly expressed in psoriatic KCs( 1). Our previous results suggest possible mechanisms for psoriasin to contribute to the development of the psoriatic lesion. Psoriasin was shown to be induced by reactive oxygen species( ROS) and its expression correlates with increased survival and NF-κB signalling in epithelial cells( 2 – 4).
Moreover, we observed that the expression of psoriasin leads to an increase in the expression of reactive oxygen species( ROS)-induced angiogenic factors and neovascularization in vitro and in mice. Psoriasin was further shown to induce the proliferation, migration and tube formation of dermal-derived endothelial cells( HMVEC-d) and to promote the release of pro-angiogenic mediators( 3, 4).
A role for psoriasin in KC differentiation was supported by the inhibited KC differentiation following psoriasin downregulation. Psoriasin was shown to correlate with the degree of KC differentiation in vivo and, using tetracycline( TET)-driven conditional psoriasin expression, we recently found a change in the regulation of differentiation genes and an expression pattern reminiscent of that in psoriatic epidermis( 5).
Cellular proliferation and apoptosis maintain tissue homeostasis, whereas dysregulated apoptosis contributes to numerous pathological conditions. In normal skin, KCs in the superficial layer of the epidermis undergo apoptosis in equilibrium with the proliferation of cells in the basal layer. The disturbed termi-
46 Forum for Nord Derm Ven 2018, Vol. 23, No. 2