Alterations of glucosylceramide-β-glucosidase levels in the skin of patients with psoriasis vulgaris
Alterations of glucosylceramide-β-glucosidase levels in the skin of patients with psoriasis vulgaris
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DOI：
10.1111/j.0022-202x.2004.23469.x
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发表时间：
2004-12-01
影响因子：
6.5
通讯作者：
Behrendt, H
中科院分区：
文献类型：
--
作者：
Alessandrini, F;Pfister, S;Behrendt, H
葡萄糖神经酰胺通过葡萄糖神经酰胺-β-葡萄糖苷酶 (GlcCer'ase) 水解产生神经酰胺，神经酰胺是介导表皮渗透屏障的细胞间层的关键成分。神经酰胺形成的紊乱被认为会影响常见皮肤病（如特应性湿疹或牛皮癣）的经皮水分流失。本研究的目的是调查寻常型银屑病受试者皮肤中的 GlcCer'ase 水平是否发生改变。从病变和非病变银屑病皮肤进行皮肤穿孔活检，并在 RNA 和蛋白质水平上评估 GlcCer'ase。手术患者的正常皮肤提供了健康受试者中 GlcCer'ase 表达的基线。我们的结果表明，在所有病例中，与正常对照相比，银屑病非病变皮肤中的 GlcCer'ase mRNA 表达均降低。有趣的是，在所有情况下，与非病变皮肤相比，病变银屑病皮肤中的 GlcCer'ase 水平均升高。对于免疫组织化学分析，我们使用新合成的抗人GBC单克隆抗体（GicCer'ase-GST融合蛋白）。结果证实，GlcCer'ase主要存在于上表皮，与正常对照相比，银屑病皮肤中的GlcCer'ase减少，与非病变银屑病皮肤相比，病变中的GlcCer'ase增加。我们的研究结果支持这样的概念，即皮损银屑病皮肤中水渗透屏障的改变可以作为GlcCer'ase等酶表达上调的触发因素，从而刺激神经酰胺的生成。
Hydrolysis of glucosylceramides by the enzyme glucosylceramide-beta-glucosidase (GlcCer'ase) results in ceramide, a critical component of the intercellular lamellae that mediates the epidermal permeability barrier. A disturbance of ceramide formation is supposed to influence the transepidermal water loss in common skin diseases like atopic eczema or psoriasis. The aim of this study was to investigate whether GlcCer'ase levels were altered in the skin of subjects with psoriasis vulgaris. Skin punch biopsies were taken from lesional and non-lesional psoriatic skin and GlcCer'ase was evaluated both at the RNA and at the protein level. Normal skin from surgical patients provided the baseline GlcCer'ase expression in healthy subjects. Our results show that GlcCer'ase mRNA expression was decreased in psoriatic non-lesional skin compared to normal controls in all cases. Interestingly, in lesional psoriatic skin the level of GlcCer'ase was increased compared to non-lesional skin in all cases. For the immunohistochemical analysis, we used a newly synthesized monoclonal antibody anti-human GBC (GicCer'ase-GST fusion protein). The results confirmed that GlcCer'ase, mainly present in the upper epidermis, was decreased in psoriatic skin compared to normal control and was increased in lesional compared to non-lesional psoriatic skin. Our findings support the concept that alteration in water permeability barrier in lesional psoriatic skin can serve as a trigger for the upregulation of the expression of enzymes like GlcCer'ase with consequent stimulation of ceramide generation.