Genome-wide transcriptional profiling of skin and dorsal root ganglia after ultraviolet-B-induced inflammation.
Genome-wide transcriptional profiling of skin and dorsal root ganglia after ultraviolet-B-induced inflammation.
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DOI：
10.1371/journal.pone.0093338
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
McMahon SB
中科院分区：
文献类型：
--
作者：
Dawes JM;Antunes-Martins A;Perkins JR;Paterson KJ;Sisignano M;Schmid R;Rust W;Hildebrandt T;Geisslinger G;Orengo C;Bennett DL;McMahon SB
紫外线B（UVB）诱导的炎症在人类和大鼠中产生剂量依赖性的机械和热痛觉过敏，最有可能通过作用于损伤部位的炎症介质。先前的工作表明，细胞因子和趋化因子的基因表达在物种之间呈正相关，并且这些因素可以促进UVB诱导的疼痛。为了研究该模型中其他潜在的疼痛介质，我们使用RNA-seq在痛觉过敏的高峰期在人类和大鼠皮肤中进行全基因组转录谱分析。此外，我们还测量了大鼠模型L4和L5 DRG中的转录变化。我们的数据表明，UVB照射在皮肤中产生大量的转录变化：2186和3888个基因在人类和大鼠皮肤中分别显著失调。人类皮肤中最高度上调的基因的特征在于编码细胞因子（IL 6和IL 24）、趋化因子（CCL 3、CCL 20、CXCL 1、CXCL 2、CXCL 3和CXCL 5）、前列腺素类合成酶考克斯-2和角蛋白基因家族成员的那些基因。总体而言，人和大鼠之间的基因表达存在强正相关和显著相关性（R = 0.8022）。 与皮肤相反，在大鼠L4和L5 DRG中仅39个基因显著失调，其中大多数具有小的倍数变化值。DRG中上调最多的基因是REG 3B、CCL 2和VGF。总体而言，我们的数据表明，许多基因在UVB照射的皮肤在人类和大鼠的痛觉过敏的高峰上调。许多最高上调的基因是细胞因子和趋化因子，再次强调了它们作为疼痛介质的潜力。然而，许多其他基因也上调，并可能在UVB诱导的痛觉过敏中发挥作用。此外，物种之间强的基因表达相关性再次强调了UVB模型作为研究炎性疼痛的翻译工具的价值。
Ultraviolet-B (UVB)-induced inflammation produces a dose-dependent mechanical and thermal hyperalgesia in both humans and rats, most likely via inflammatory mediators acting at the site of injury. Previous work has shown that the gene expression of cytokines and chemokines is positively correlated between species and that these factors can contribute to UVB-induced pain. In order to investigate other potential pain mediators in this model we used RNA-seq to perform genome-wide transcriptional profiling in both human and rat skin at the peak of hyperalgesia. In addition we have also measured transcriptional changes in the L4 and L5 DRG of the rat model. Our data show that UVB irradiation produces a large number of transcriptional changes in the skin: 2186 and 3888 genes are significantly dysregulated in human and rat skin, respectively. The most highly up-regulated genes in human skin feature those encoding cytokines (IL6 and IL24), chemokines (CCL3, CCL20, CXCL1, CXCL2, CXCL3 and CXCL5), the prostanoid synthesising enzyme COX-2 and members of the keratin gene family. Overall there was a strong positive and significant correlation in gene expression between the human and rat (R = 0.8022). In contrast to the skin, only 39 genes were significantly dysregulated in the rat L4 and L5 DRGs, the majority of which had small fold change values. Amongst the most up-regulated genes in DRG were REG3B, CCL2 and VGF. Overall, our data shows that numerous genes were up-regulated in UVB irradiated skin at the peak of hyperalgesia in both human and rats. Many of the top up-regulated genes were cytokines and chemokines, highlighting again their potential as pain mediators. However many other genes were also up-regulated and might play a role in UVB-induced hyperalgesia. In addition, the strong gene expression correlation between species re-emphasises the value of the UVB model as translational tool to study inflammatory pain.
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影响因子：
17.1
作者：
Dawes JM;Calvo M;Perkins JR;Paterson KJ;Kiesewetter H;Hobbs C;Kaan TK;Orengo C;Bennett DL;McMahon SB
通讯作者：
McMahon SB
影响因子：
7.3
作者：
CUNHA, FQ;POOLE, S;FERREIRA, SH
通讯作者：
FERREIRA, SH
影响因子：
7
作者：
Hammer, Paul;Banck, Michaela S.;Beutler, Andreas S.
通讯作者：
Beutler, Andreas S.
DOI：
10.1053/eujp.1998.0106
发表时间：
1999-01-01
期刊：
EUROPEAN JOURNAL OF PAIN-LONDON
影响因子：
--
作者：
Hoffmann, RT;Schmelz, M
通讯作者：
Schmelz, M
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y