Transcriptome analysis to identify the downstream genes of androgen receptor in dermal papilla cells.

Transcriptome analysis to identify the downstream genes of androgen receptor in dermal papilla cells.
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DOI:
10.1186/s12863-021-01018-6
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发表时间:
2022-01-04
期刊:
影响因子:
1.9
通讯作者:
Fukuda T
Fukuda T
中科院分区:
生物学3区
文献类型:
--
作者:
Furuya K;Fujibayashi S;Wu T;Takahashi K;Takase S;Orimoto A;Sugano E;Tomita H;Kashiwagi S;Kiyono T;Ishii T;Fukuda T

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睾酮信号转导介导多种疾病,如雄激素性脱发和前列腺癌。睾酮信号传导由雄激素受体(AR)介导。在这项研究中,我们偶然发现,原代和永生化的毛乳头细胞抑制AR的表达,虽然毛乳头细胞表达AR在体内。为了分析AR信号通路,我们通过逆转录病毒将AR基因外源性引入永生化毛乳头细胞,并全面比较了它们在有和没有AR表达的情况下的表达谱。全转录组分析显示,粘着斑途径主要受AR信号的激活影响。特别是,我们发现,小窝蛋白-1基因表达下调AR表达细胞,表明小窝蛋白-1是由AR控制。我们的全转录组数据是发现睾酮相关疾病新治疗靶点的关键资源。在线版本包含补充材料,可通过10.1186/s12863-021-01018-6获得。对AR阴性和AR阳性毛乳头细胞进行RNA-Seq分析,获得完整的基因表达谱。生物信息学分析表明,caveolin-1和EGF受体是AR信号的下游。我们的研究表明,精确突变细胞和整体转录组的组合是有效的,以确定下游基因。在线版本包含补充材料,可通过10.1186/s12863-021-01018-6获得。
Testosterone signaling mediates various diseases, such as androgenetic alopecia and prostate cancer. Testosterone signaling is mediated by the androgen receptor (AR). In this study, we fortuitously found that primary and immortalized dermal papilla cells suppressed AR expression, although dermal papilla cells express AR in vivo. To analyze the AR signaling pathway, we exogenously introduced the AR gene via a retrovirus into immortalized dermal papilla cells and comprehensively compared their expression profiles with and without AR expression. Whole-transcriptome profiling revealed that the focal adhesion pathway was mainly affected by the activation of AR signaling. In particular, we found that caveolin-1 gene expression was downregulated in AR-expressing cells, suggesting that caveolin-1 is controlled by AR. Our whole transcriptome data is critical resources for discovery of new therapeutic targets for testosterone-related diseases. The online version contains supplementary material available at 10.1186/s12863-021-01018-6. The comprehensive gene expression profiling were obtained by RNA-Seq analysis about AR negative and AR positive dermal papilla cells. The bioinformatics analysis suggested that caveolin-1 and EGF receptors are the downstream of AR signaling. Our study showed the combination of pinpoint mutant cells and global transcriptome is effective to identify the downstream genes. The online version contains supplementary material available at 10.1186/s12863-021-01018-6.
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