Transcriptomic profiling of dorsal root ganglia in atopic and healthy dogs: A comparative RNA sequencing study with implications in cutaneous itch research.

Abstract

Background: 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).

Animals: Two atopic and four healthy dogs.

Materials and methods: DRGs were collected from atopic and healthy dogs to compare their transcriptional profiles using RNA sequencing.

Results: 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.

Conclusions and clinical relevance: Our study suggested that dysregulation of neuroinflammatory pathways might play a role in the pathomechanism of cAD as in humans.