Lack of evidence for activation of the hedgehog pathway in psoriasis.
Lack of evidence for activation of the hedgehog pathway in psoriasis.
复制标题
DOI：
10.1038/jid.2008.266
复制
发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
最近的报道表明，刺猬（Hh）途径在皮损银屑病皮肤中被激活，用Hh途径拮抗剂环巴胺治疗可能导致疾病的快速解决。为了评估Hh通路在银屑病中的活性，我们从58名银屑病患者的皮损和未受累皮肤以及63名正常对照受试者中分离RNA，并将这些样品在Affytechnology HU 133 Plus 2.0基因阵列上进行全局基因表达谱分析。我们对Hh靶基因（PTCH 1和GLI 1）特别感兴趣，这些基因的表达在Hh信号转导中升高。微阵列数据显示PTCH 1表达在未受累和病变皮肤中下调（分别为1.1倍和2倍，p<0.0001）。此外，GLI 1 mRNA在病变皮肤中下调（1.7倍p<0.05）。对于Hh配体或Smoothened（SMO），在病变和未受累皮肤之间未观察到显著变化。QT-PCR证实了这些发现。原位杂交GLI 1和PTCH 1在基底细胞癌肿瘤细胞中呈阳性，但在未受累或皮损的银屑病皮肤中可忽略不计。在银屑病皮损中Hh靶基因表达升高的情况表明Hh通路在这种疾病中没有被激活，这就提出了关于Hh拮抗剂作为抗银屑病药物的建议用途的问题。
Recent reports have suggested that the Hedgehog (Hh) pathway is activated in lesional psoriatic skin, and that treatment with the Hh pathway antagonist cyclopamine may lead to rapid resolution of the disease. To assess Hh pathway activity in psoriasis, we isolated RNA from lesional and uninvolved skin of 58 psoriatic patients, and from 63 normal control subjects, and subjected these samples to global gene expression profiling on Affymetrix HU133 Plus 2.0 gene arrays. We were especially interested in Hh target genes (PTCH1, and GLI1), whose expression is elevated in response to Hh signaling. The microarray data demonstrated down-regulation of PTCH1 expression in uninvolved and lesional skin (1.1-fold and 2-fold respectively, p<0.0001). Additionally GLI1 mRNA was down-regulated in lesional skin (1.7 fold p<0.05). No significant changes were observed between lesional and uninvolved skin for the Hh ligands or Smoothened (SMO). QT-PCR confirmed these findings. In situ hybridization for GLI1 and PTCH1 was positive in BCC tumor cells, but was negligible in uninvolved or lesional psoriatic skin. The absence of elevated Hh target gene expression in lesional psoriatic skin indicates that the Hh pathway is not activated in this disease, raising questions regarding the proposed use of Hh antagonists as anti-psoriatic agents.
登录
查看更多内容
影响因子：
3.5
作者：
Bowcock, AM;Shannon, W;Menter, A
通讯作者：
Menter, A
影响因子：
10.3
作者：
Endo, H;Momota, Y;Shinkai, H
通讯作者：
Shinkai, H
DOI：
10.1083/jcb.147.1.71
发表时间：
1999-10-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fan H;Khavari PA
通讯作者：
Khavari PA
影响因子：
6
作者：
Allen, M;Grachtchouk, M;Dlugosz, AA
通讯作者：
Dlugosz, AA
影响因子：
6.5
作者：
Johansen, C;Flindt, E;Iversen, L
通讯作者：
Iversen, L