[HTML][HTML] A role for TGFβ signaling in the pathogenesis of psoriasis

G Han, CA Williams, K Salter, PJ Garl, AG Li… - Journal of investigative …, 2010 - Elsevier
G Han, CA Williams, K Salter, PJ Garl, AG Li, XJ Wang
Journal of investigative dermatology, 2010Elsevier
Deregulation of transforming growth factor-β (TGFβ) signaling has been reported in human
psoriasis. Our recent study using a keratin 5 promoter (K5. TGFβ1 wt) showed that
transgenic mice expressing wild-type TGFβ1 in the epidermis developed severe skin
inflammation. Additional experimental data further support a direct role for TGFβ1
overexpression in skin inflammation. First, we temporally induced TGFβ1 expression in
keratinocytes in our gene-switch TGFβ1 wt transgenic mice and found inflammation severity …
Deregulation of transforming growth factor-β (TGFβ) signaling has been reported in human psoriasis. Our recent study using a keratin 5 promoter (K5.TGFβ1wt) showed that transgenic mice expressing wild-type TGFβ1 in the epidermis developed severe skin inflammation. Additional experimental data further support a direct role for TGFβ1 overexpression in skin inflammation. First, we temporally induced TGFβ1 expression in keratinocytes in our gene-switch TGFβ1wt transgenic mice and found inflammation severity correlated with TGFβ1wt transgene expression. Second, deletion of T cells in K5.TGFβ1wt mice significantly delayed skin inflammation and associated epidermal hyperplasia/hyperkeratosis. Third, therapeutic approaches effective for human psoriasis, that is, Etanercept and Rosiglitazone, are effective in alleviating the symptoms observed in K5.TGFβ1wt mice. Future studies will analyze specific mechanisms and identify key factors in TGFβ1-induced skin inflammation. Our mouse models will provide a useful tool for understanding the molecular mechanisms of inflammatory skin disorders in which TGFβ1 is overexpressed.
Elsevier