Skip to main content

role of a small GTPase, RhoA, in skin inflammation

Objective

Psoriasis is a common immune-mediated disease, characterized by aberrant epidermal differentiation, surface scale formation and marked cutaneous inflammation. It affects about 1% of the European population and has currently no effective treatment. The visible nature of the disease ensures that patients have both physical and psychosocial effects intruding their life style. Using genetically modified mice, engineered to have a keratinocyte-restricted deletion of the RhoA gene, we found for the first time that RhoA regulates the sensitivity of skin to inflammatory stress in vivo. Moreover, around a metal ear tag, those mice develop a severe skin defect bearing similarities to psoriasis. Our goal is to understand the role of RhoA in skin inflammation and the possible involvement of decreased RhoA signaling in the development of psoriasis. To achieve our goal we propose to investigate gene expression in vivo through an array on freshly prepared primary keratinocytes and to test if the induced gene expression is cell autonomous by using a lentivirus strategy. A lentiviral knockdown sublibrary will help us to determine which signaling mechanisms contribute to those changes in gene expression. Moreover, we want to use our model to investigate the sensitivity of RhoA null skin to an irritant contact dermatis model and to induce an allergic contact dermatis. We will then analyze the infiltrating cells and determine the mechanisms involved in the inflammation. Using tissue sections from our mice and from psoriasis patients we will study the similarities between ear tag lesions and psoriatic lesions by establishing new immunostaining protocols. Our work will increase our understanding of psoriasis development and identify new drug targets that are needed to improve the current psoriasis therapies.

Call for proposal

FP7-PEOPLE-2009-RG
See other projects for this call

Coordinator

KOBENHAVNS UNIVERSITET
Address
Norregade 10
1165 Kobenhavn
Denmark
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 100 000
Administrative Contact
Ivan Kristoffersen (Mr.)