Exploring neuronal mechanisms involved in the scratching behavior of a mouse model of allergic contact dermatitis by transcriptomics

Cellular & Molecular Biology Letters

Yan Tai¹  Junfan Fang²  Huimin Nie²  Xiaomei Shao²  Jianqiao Fang²  Boyi Liu²  Danyi Zeng²  Chengyu Yin²  Jie Wang²  Junying Du²  Boyu Liu²  Yi Liang²  Yuanyuan Li²  Ruixiang Chen³ 

[1] Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China;Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, 310053, Hangzhou, China;Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, 310053, Hangzhou, China;The First Department of Acupuncture, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an, Shaanxi, China;

关键词: Itch;    Pain;    Sensory neurons;    Allergic contact dermatitis;    RNA-seq;   

DOI  :  10.1186/s11658-022-00316-w

来源: Springer

【 摘 要 】

BackgroundAllergic contact dermatitis (ACD) is a common skin condition characterized by contact hypersensitivity to allergens, accompanied with skin inflammation and a mixed itch and pain sensation. The itch and pain dramatically affects patients’ quality of life. However, still little is known about the mechanisms triggering pain and itch sensations in ACD.MethodsWe established a mouse model of ACD by sensitization and repetitive challenge with the hapten oxazolone. Skin pathological analysis, transcriptome RNA sequencing (RNA-seq), qPCR, Ca2+ imaging, immunostaining, and behavioral assay were used for identifying gene expression changes in dorsal root ganglion innervating the inflamed skin of ACD model mice and for further functional validations.ResultsThe model mice developed typical ACD symptoms, including skin dryness, erythema, excoriation, edema, epidermal hyperplasia, inflammatory cell infiltration, and scratching behavior, accompanied with development of eczematous lesions. Transcriptome RNA-seq revealed a number of differentially expressed genes (DEGs), including 1436-DEG mRNAs and 374-DEG-long noncoding RNAs (lncRNAs). We identified a number of DEGs specifically related to sensory neuron signal transduction, pain, itch, and neuroinflammation. Comparison of our dataset with another published dataset of atopic dermatitis mouse model identified a core set of genes in peripheral sensory neurons that are exclusively affected by local skin inflammation. We further found that the expression of the pain and itch receptor MrgprD was functionally upregulated in dorsal root ganglia (DRG) neurons innervating the inflamed skin of ACD model mice. MrgprD activation induced by its agonist β-alanine resulted in exaggerated scratching responses in ACD model mice compared with naïve mice.ConclusionsWe identified the molecular changes and cellular pathways in peripheral sensory ganglia during ACD that might participate in neurogenic inflammation, pain, and itch. We further revealed that the pain and itch receptor MrgprD is functionally upregulated in DRG neurons, which might contribute to peripheral pain and itch sensitization during ACD. Thus, targeting MrgprD may be an effective method for alleviating itch and pain in ACD.

【 授权许可】

CC BY