Systematic screening and identification of novel psoriasis-specific genes from the transcriptome of psoriasis-like keratinocytes
Systematic screening and identification of novel psoriasis-specific genes from the transcriptome of psoriasis-like keratinocytes
复制标题
从银屑病样角质形成细胞转录组中系统筛选和鉴定新型银屑病特异性基因
DOI：
10.3892/mmr.2018.9782
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发表时间：
2019-03-01
影响因子：
3.4
通讯作者：
Li, Jiong
中科院分区：
文献类型：
--
作者：
Wang, Zhen;Zheng, Huaping;Li, Jiong
牛皮癣是一种慢性炎症性皮肤病。角质形成细胞（Keratinocytes，KCs）作为皮肤特异性细胞，在银屑病的免疫发病机制中起重要作用。在本研究中，来自银屑病样KC的转录组数据与银屑病患者皮肤/表皮的已报道的转录组数据一起使用，排除已知的银屑病相关基因，这些基因在先前的研究中已经根据GeneCards数据库进行了很好的描述，以筛选新的银屑病相关基因。根据UniGene数据集的人类表达序列标签，位于银屑病相关位点附近的6个基因在皮肤中高表达。其中4个基因（epiregulin，NIPA like domain containing 4，serpin family B member 7和WAP four-disulfide core domain 12）在正常小鼠表皮（主要是KC）和银屑病小鼠表皮细胞中高表达，而在银屑病真皮细胞中不表达，进一步说明了这些基因的特异性。此外，在全身炎症反应综合征（SIRS）中，SERPINB 7在来自SIRS和对照小鼠的免疫活化组织中的表达没有差异。研究还发现，银屑病患者皮损皮肤中SERPINB的mRNA表达水平显著高于同一患者的非皮损银屑病皮肤。SERPINB 7可能是进一步研究的有价值的候选者。在本研究中，提出了一种鉴定新的关键致病性皮肤特异性分子的方法，该方法可用于研究和治疗银屑病。
Psoriasis is a chronic inflammatory skin disease. Keratinocytes (KCs), as skin-specific cells, serve an important role in the immunopathogenesis of psoriasis. In the present study, transcriptome data derived from psoriasis-like KCs were used together with the reported transcriptome data from the skin/epidermis of patient with psoriasis, excluding known psoriasis-associated genes that have been well described in the previous studies according to GeneCards database, to screen for novel psoriasis-associated genes. According to the human expressed sequence tag of UniGene dataset, six genes that are located near psoriasis-associated loci were highly expressed in skin. Among these six genes, four genes (epiregulin, NIPA like domain containing 4, serpin family B member 7 and WAP four-disulfide core domain 12) were highly expressed in normal mouse epidermis (mainly KCs) and mouse psoriatic epidermis cells, but not in psoriatic dermis cells, which further emphasized the specificity of these genes. Furthermore, in systemic inflammatory response syndrome (SIRS), SERPINB7 showed no difference in expression in immune-activated tissues from SIRS and control mice. It was also found that the mRNA expression levels of SERPINB in lesional skin of patients with psoriasis were significantly higher than in non-lesional psoriatic skin from the same patients. SERPINB7 may be a valuable candidate for further studies. In the present study, a method for identifying novel key pathogenic skin-specific molecules is presented, which may be used for investigating and treating psoriasis.