Department of Pathology, University of Colorado Denver, Aurora, Colorado 80045, USA.
J Invest Dermatol. 2010 Feb;130(2):371-7. doi: 10.1038/jid.2009.252. Epub 2009 Aug 27.
Deregulation of transforming growth factor-beta (TGFbeta) signaling has been reported in human psoriasis. Our recent study using a keratin 5 promoter (K5.TGFbeta1(wt)) showed that transgenic mice expressing wild-type TGFbeta1 in the epidermis developed severe skin inflammation. Additional experimental data further support a direct role for TGFbeta1 overexpression in skin inflammation. First, we temporally induced TGFbeta1 expression in keratinocytes in our gene-switch TGFbeta1(wt) transgenic mice and found inflammation severity correlated with TGFbeta1(wt) transgene expression. Second, deletion of T cells in K5.TGFbeta1(wt) 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.TGFbeta1(wt) mice. Future studies will analyze specific mechanisms and identify key factors in TGFbeta1-induced skin inflammation. Our mouse models will provide a useful tool for understanding the molecular mechanisms of inflammatory skin disorders in which TGFbeta1 is overexpressed.
转化生长因子-β（TGF-β）信号的失调已在人类银屑病中报道。我们最近使用角蛋白 5 启动子（K5.TGFβ1（wt））的研究表明，在表皮中表达野生型 TGF-β1 的转基因小鼠会发展出严重的皮肤炎症。额外的实验数据进一步支持 TGF-β1 过表达在皮肤炎症中的直接作用。首先，我们在基因开关 TGF-β1（wt）转基因小鼠中的角蛋白细胞中瞬时诱导 TGF-β1 表达，发现炎症严重程度与 TGF-β1（wt）转基因表达相关。其次，在 K5.TGFβ1（wt）小鼠中删除 T 细胞可显著延迟皮肤炎症和相关的表皮过度增生/过度角化。第三，对人类银屑病有效的治疗方法，即依那西普和罗格列酮，可有效缓解 K5.TGFβ1（wt）小鼠中观察到的症状。未来的研究将分析特定的机制，并确定 TGF-β1 诱导的皮肤炎症中的关键因素。我们的小鼠模型将为理解 TGF-β1 过表达的炎症性皮肤疾病的分子机制提供有用的工具。
