Psoriatic skin expresses the transcription factor Gli1: possible contribution of decreased neurofibromin expression
Psoriatic skin expresses the transcription factor Gli1: possible contribution of decreased neurofibromin expression
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DOI：
10.1111/j.1365-2133.2005.06975.x
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发表时间：
2006-04-01
影响因子：
10.3
通讯作者：
Shinkai, H
中科院分区：
文献类型：
--
作者：
Endo, H;Momota, Y;Shinkai, H
银屑病是一种以角质形成细胞过度增殖为特征的慢性炎症性皮肤病。诱导角质形成细胞过度增殖的细胞内信号通路仍有待阐明。Hedgehog（Hh）信号传导抑制剂环巴胺（cyclopamine）最近被报道可清除银屑病皮肤病变，表明Hh信号传导通路参与了病变角质形成细胞的过度增殖。我们以前已经观察到激活的Hh信号通路的施万细胞丛状神经纤维瘤1型神经纤维瘤（NF 1），这是由于功能丧失的NF 1编码蛋白，神经纤维蛋白。在银屑病中，神经纤维蛋白表达的缺陷已被观察到在病变keratinocytes.Objectives的Hh信号通路是否会被激活，在银屑病和是否抑制神经纤维蛋白的表达会增强激活的Hh信号pathway.Methods激活的Hh信号通路的蛋白表达的靶基因之一，GLI 1，编码的转录因子Gli 1。用标准免疫过氧化物酶技术对7个银屑病皮肤样本和7个对照正常皮肤样本进行免疫组织化学研究。用逆转录-聚合酶链反应（RT-PCR）检测转染NF 1双链小干扰RNA（siRNA）的HaCaT细胞中GLI 1 mRNA的表达。结果银屑病患者皮肤中GLI 1 mRNA表达阳性，正常对照皮肤中GLI 1 mRNA表达阴性。抑制HaCaT细胞中神经纤维蛋白的表达可上调GLI 1的mRNA表达。结论银屑病患者Hh信号通路被激活，神经纤维蛋白缺乏可上调该通路。
Background Psoriasis is a chronic inflammatory disorder of skin characterized by hyperproliferation of keratinocytes. Intracellular signalling pathways inducing the hyperproliferation of keratinocytes remain to be elucidated. An inhibitor of Hedgehog (Hh) signalling, cyclopamine, was recently reported to clear psoriatic skin lesions, suggesting involvement of the Hh signalling pathway in the hyperproliferation of lesional keratinocytes. We have previously observed activation of the Hh signalling pathway in Schwann cells of plexiform neurofibroma in neurofibromatosis type 1 (NF1), which results from functional loss of the NF1 encoding protein, neurofibromin. In psoriasis, deficiency of neurofibromin expression has been observed in lesional keratinocytes.Objectives To investigate whether the Hh signalling pathway would be activated in psoriasis and whether inhibition of neurofibromin expression would enhance the activation of the Hh signalling pathway.Methods Activation of the Hh signalling pathway was examined by protein expression of one of the target genes, GLI1, coding for the transcription factor Gli1. Immunohistochemical studies were performed on seven psoriatic skin samples and seven control normal skin samples with a standard immunoperoxidase technique. mRNA expression of GLI1 was analysed by reverse transcriptase-polymerase chain reaction in HaCaT cells transfected with double-strand small interfering RNA for NF1.Results Our results showed Gli1 expression in psoriatic skin but not in control normal skin. Inhibition of neurofibromin expression in HaCaT cells upregulated mRNA expression of GLI1.Conclusions Our findings indicate that the Hh signalling pathway is activated in psoriasis and that neurofibromin deficiency may upregulate the pathway.