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Induction of differentiation in psoriatic keratinocytes by propylthiouracil and fructose

机译:丙基硫尿嘧啶和果糖诱导银屑病角质形成细胞分化

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Psoriasis is characterized by uncontrolled proliferation and poor differentiation. Sirtuin1 (SIRT1) a class III deacetylase, crucial for differentiation in normal keratinocytes, is reduced in psoriasis. Down regulated SIRT1 levels may contribute to poor differentiation in psoriasis. In addition, the levels of early differentiation factors Keratin1 (K1) and Keratin10 (K10) are depleted in psoriasis. We attempted to study a possible effect of fructose, a SIRT1 upregulator and Propylthiouracil (PTU) to augment differentiation in psoriatic keratinocytes. Keratinocytes were cultured from lesional biopsies obtained from psoriatic patients and control cells were obtained from patients undergoing abdominoplasty. Cells were treated with fructose and PTU individually. K1 and K10 transcript levels were measured to evaluate early differentiation; SIRT1 protein expression was also studied to decipher its role in the mechanism of differentiation. The K1, K10 transcript levels, SIRT1 protein and transcript levels in fructose treated psoriatic keratinocytes were improved. This suggests keratinocyte differentiation was induced by fructose through SIRT1 upregulation. Whereas PTU induced differentiation, as confirmed by improved K1, K10 transcript levels followed a non-SIRT1 mechanism. We conclude that the use of fructose and PTU may be an adjunct to the existing therapies for psoriasis.
机译:银屑病的特征是不受控制的增殖和差的分化。 Sirtuin1(SIRT1)是一种III类脱乙酰基酶,对正常角质形成细胞的分化至关重要,在牛皮癣中会减少。下调的SIRT1水平可能会导致牛皮癣的不良分化。此外,牛皮癣的早期分化因子Keratin1(K1)和Keratin10(K10)的水平也被消耗掉。我们试图研究果糖,SIRT1上调剂和丙硫氧嘧啶(PTU)增强银屑病角质形成细胞分化的可能作用。从牛皮癣患者的病灶活检中培养角质形成细胞,而从腹部整形术患者获得对照细胞。细胞分别用果糖和PTU处理。测量K1和K10转录水平以评估早期分化;还研究了SIRT1蛋白的表达,以解释其在分化机制中的作用。果糖处理的牛皮癣角质形成细胞中的K1,K10转录水平,SIRT1蛋白和转录水平得到改善。这表明果糖通过SIRT1上调诱导了角质形成细胞的分化。尽管PTU诱导了分化,如改善的K1所证实,但K10转录水平遵循非SIRT1机制。我们得出结论,果糖和PTU的使用可能是牛皮癣现有疗法的辅助手段。

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