Itch-associated peptides: RNA-Seq and bioinformatic analysis of natriuretic precursor peptide B and gastrin releasing peptide in dorsal root and trigeminal ganglia, and the spinal cord.
Itch-associated peptides: RNA-Seq and bioinformatic analysis of natriuretic precursor peptide B and gastrin releasing peptide in dorsal root and trigeminal ganglia, and the spinal cord.
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DOI：
10.1186/1744-8069-10-44
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发表时间：
2014-08-14
期刊：
影响因子：
3.3
通讯作者：
Iadarola MJ
中科院分区：
文献类型：
--
作者：
Goswami SC;Thierry-Mieg D;Thierry-Mieg J;Mishra S;Hoon MA;Mannes AJ;Iadarola MJ
已经提出三种神经肽，胃泌素释放肽（GRP）、尿钠前体肽B（NPP B）和神经介肽B（NMB）在瘙痒感觉中起作用。然而，表达这些肽的组织及其在瘙痒回路中的位置最近成为争论的主题。在这里，我们使用下一代RNA-Seq来检查DRG、三叉神经节和脊髓中编码GRP、NPPB、NMB和其他肽的转录物的表达，以及这些组织中其同源受体的表达水平。RNA-Seq证明GRP在小鼠、大鼠或人类感觉神经节中不转录。激活利钠肽受体1（NPR 1）的NPPB在小鼠DRG中表达良好，在大鼠和人类中表达较少，而也作用于NPR 1受体的NPPA在所有三种物种中表达。对小鼠、大鼠和人类脊髓中表达的转录本的分析显示Nppb没有表达，但明确检测到Grp和GRP受体（Grpr）的表达。编码NMB和速激肽肽的转录物在DRG中是最高表达的。使用用于产生GRP抗体的肽序列与蛋白质组数据库的生物信息学比较显示，NMB和P物质的C-末端一级序列可以潜在地解释来自先前研究的结果，该研究显示DRG中的GRP免疫染色。RNA-Seq证实了NPPB在小鼠中的主要瘙痒传入作用以及NPPB和NPPA在大鼠和人类中的潜在作用，但不支持GRP作为小鼠、大鼠或人类中的主要瘙痒神经递质。因此，我们的结果与Sun和Chen（2007）最初提出的GRP在DRG中表达的观点不一致。相比之下，我们的数据强烈支持瘙痒途径，其中GRP的瘙痒诱导作用是通过其从脊髓神经元释放来发挥的。
Three neuropeptides, gastrin releasing peptide (GRP), natriuritic precursor peptide B (NPPB), and neuromedin B (NMB) have been proposed to play roles in itch sensation. However, the tissues in which these peptides are expressed and their positions in the itch circuit has recently become the subject of debate. Here we used next-gen RNA-Seq to examine the expression of transcripts coding for GRP, NPPB, NMB, and other peptides in DRG, trigeminal ganglion, and the spinal cord as well as expression levels for their cognate receptors in these tissues. RNA-Seq demonstrates that GRP is not transcribed in mouse, rat, or human sensory ganglia. NPPB, which activates natriuretic peptide receptor 1 (NPR1), is well expressed in mouse DRG and less so in rat and human, whereas NPPA, which also acts on the NPR1 receptor, is expressed in all three species. Analysis of transcripts expressed in the spinal cord of mouse, rat, and human reveals no expression of Nppb, but unambiguously detects expression of Grp and the GRP-receptor (Grpr). The transcripts coding for NMB and tachykinin peptides are among the most highly expressed in DRG. Bioinformatics comparisons using the sequence of the peptides used to produce GRP-antibodies with proteome databases revealed that the C-terminal primary sequence of NMB and Substance P can potentially account for results from previous studies which showed GRP-immunostaining in the DRG. RNA-Seq corroborates a primary itch afferent role for NPPB in mouse and potentially NPPB and NPPA in rats and humans, but does not support GRP as a primary itch neurotransmitter in mouse, rat, or humans. As such, our results are at odds with the initial proposal of Sun and Chen (2007) that GRP is expressed in DRG. By contrast, our data strongly support an itch pathway where the itch-inducing actions of GRP are exerted through its release from spinal cord neurons.
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DOI：
10.1111/j.1742-4658.2011.08083.x
发表时间：
2011-06
期刊：
The FEBS journal
影响因子：
--
作者：
Misono KS;Philo JS;Arakawa T;Ogata CM;Qiu Y;Ogawa H;Young HS
通讯作者：
Young HS
影响因子：
2.5
作者：
Moser, Hannah R.;Giesler, Glenn J., Jr.
通讯作者：
Giesler, Glenn J., Jr.
影响因子：
3.3
作者：
Liu XY;Wan L;Huo FQ;Barry DM;Li H;Zhao ZQ;Chen ZF
通讯作者：
Chen ZF
影响因子：
11.4
作者：
Mishra, Santosh K.;Tisel, Sarah M.;Hoon, Mark A.
通讯作者：
Hoon, Mark A.
影响因子：
7
作者：
Hammer, Paul;Banck, Michaela S.;Beutler, Andreas S.
通讯作者：
Beutler, Andreas S.