Tamamoto-Mochizuki Chie, Mishra Santosh K
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
Vet Dermatol. 2025 Aug;36(4):401-411. doi: 10.1111/vde.13324. Epub 2025 Jan 27.
Itch is a common clinical sign in skin disorders. While the neural pathways of itch transmission from the skin to the brain are well understood in rodents, the same pathways in dogs remain unclear. The knowledge gap hinders the development of effective treatments for canine itch-related disorders.
HYPOTHESIS/OBJECTIVES: This study aimed to investigate the differential gene expression in the dorsal root ganglia (DRGs) between healthy and atopic dogs to identify specific molecules potentially involved in itch signalling and neuroinflammation in canine atopic dermatitis (cAD).
Two atopic and four healthy dogs.
DRGs were collected from atopic and healthy dogs to compare their transcriptional profiles using RNA sequencing.
Principal component and heatmap analyses revealed two distinct clusters separating atopic from healthy dogs. Consistent with this observation, we identified 627 (543 upregulated and 84 downregulated) differentially expressed genes (DEGs) in atopic compared with healthy dogs. We further narrowed down our genes of interest to common DEGs in each atopic dog, which revealed 159 (132 upregulated and 27 downregulated) DEGs. Among these genes, when we focused on itch signalling-associated molecules, P2RY12, IL-2RG, TLR1 and POSTN were significantly upregulated, while MRGPRD and LPAR3 were both significantly downregulated in atopic dogs compared with those in healthy dogs. Pathway analysis showed a significant upregulation of CREB signalling in neurons, myelination signalling and neuroinflammation signalling pathways in atopic dogs.
Our study suggested that dysregulation of neuroinflammatory pathways might play a role in the pathomechanism of cAD as in humans.
瘙痒是皮肤疾病常见的临床症状。虽然在啮齿动物中，从皮肤到大脑的瘙痒传导神经通路已得到充分了解，但犬类的相同通路仍不清楚。这一知识空白阻碍了犬类瘙痒相关疾病有效治疗方法的开发。
假设/目的：本研究旨在调查健康犬和特应性犬背根神经节（DRG）中的差异基因表达，以确定可能参与犬特应性皮炎（cAD）瘙痒信号传导和神经炎症的特定分子。
两只特应性犬和四只健康犬。
从特应性犬和健康犬收集DRG，使用RNA测序比较它们的转录谱。
主成分分析和热图分析显示，特应性犬和健康犬分为两个不同的聚类。与该观察结果一致，我们在特应性犬中鉴定出627个（543个上调和84个下调）差异表达基因（DEG），与健康犬相比。我们进一步将感兴趣的基因缩小到每只特应性犬中的常见DEG，结果显示有159个（132个上调和27个下调）DEG。在这些基因中，当我们关注与瘙痒信号相关的分子时，与健康犬相比，特应性犬中的P2RY12、IL - 2RG、TLR1和POSTN显著上调，而MRGPRD和LPAR3均显著下调。通路分析显示，特应性犬的神经元中CREB信号通路、髓鞘形成信号通路和神经炎症信号通路显著上调。
我们的研究表明，神经炎症通路失调可能在cAD的发病机制中起作用，如同在人类中一样。
