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首页> 外文期刊>EMBO Journal >Latent TGF beta 1 overexpression in keratinocytes results in a severe psoriasis-like skin disorder
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Latent TGF beta 1 overexpression in keratinocytes results in a severe psoriasis-like skin disorder

机译:潜在的转化生长因子β1过度角化细胞导致严重psoriasis-like皮肤病

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摘要

Transforming growth factor beta1 (TGFbeta1), a potent keratinocyte growth inhibitor, has been shown to be overexpressed in keratinocytes in certain inflammatory skin diseases and has been thought to counteract the effects of other growth factors at the site of inflammation. Surprisingly, our transgenic mice expressing wild-type TGFb1 in the epidermis using a keratin 5 promoter (K5.TGFbeta1(wt)) developed inflammatory skin lesions, with gross appearance of psoriasis-like plaques, generalized scaly erythema, and Koebner's phenomenon. These lesions were characterized by epidermal hyperproliferation, massive infiltration of neutrophils, T lymphocytes, and macrophages to the epidermis and superficial dermis, subcorneal microabscesses, basement membrane degradation, and angiogenesis. K5.TGFbeta1(wt) skin exhibited multiple molecular changes that typically occur in human Th1 inflammatory skin disorders, such as psoriasis. Further analyses revealed enhanced Smad signaling in transgenic epidermis and dermis. Our study suggests that certain pathological condition-induced TGFb1 overexpression in the skin may synergize with or induce molecules required for the development of Th1 inflammatory skin disorders.
机译:转化生长因子beta1 (TGFbeta1)强有力的角化细胞生长抑制剂,一直角化细胞中过表达某些炎症皮肤病和认为抵消其他增长的影响因素的炎症。令人惊讶的是,我们的转基因小鼠表达野生型的TGFb1表皮角蛋白5促进剂(K5.TGFbeta1 (wt))炎症性皮肤损伤,其外观psoriasis-like斑块,广义鳞状红斑,Koebner现象。是由表皮特征增生,大规模的渗透中性粒细胞、T淋巴细胞和巨噬细胞表皮和真皮浅,subcorneal微小脓肿,基底膜降解,和血管生成。多个分子通常会发生变化在人类Th1炎症性皮肤疾病,如牛皮癣。Smad转基因表皮和信号真皮。病理condition-induced TGFb1皮肤可能协同或超表达诱导分子的发展所需Th1炎症性皮肤病。

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