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749 Transcriptome Analysis of Dorsal Root Ganglion in Atopic Dermatitis-Induced Mice Reveals Potential Biomarker for Atopic Dermatitis

˜The œjournal of investigative dermatology/Journal of investigative dermatology(2022)

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摘要
Itch is a typical symptom that exacerbates atopic dermatitis (AD) and is associated with both the central and peripheral nervous systems. In a previous study, pruritogen mediators (histamine, serotonin, substance P, interleukin 31, and thymic stromal lymphopoietin) secreted in the skin bind to their receptors located on somatosensory neurons to transmit itch signals to the brain. In this study, we aimed to elucidate the profile of dorsal root ganglion (DRG), which contains the cell bodies of sensory neurons, from AD mice compared to DRG from control mice. We performed RNA seq analyses and used DESeq2 and Caret R packages for the differentially expressed gene (DEG) and random forest analyses, respectively. A total of 142 DEGs between the control and severe AD mice group were identified. These changed genes were mainly enriched in the GO function related to positive regulation of inflammatory response, leukocyte migration involved in the inflammatory response, and cell adhesion. Also, a total of 87 between the mild AD and severe AD mice group were identified. These changed genes were mainly enriched in the GO function related to inflammatory response, positive regulation of inflammatory response, and cellular oxidant detoxification. In particular, brain-derived neurotrophic factor (Bdnf) and stimulator of interferon genes (Sting) were most distinctly upregulated in the severe AD mice group. Moreover, the expressions of these genes gradually increased in the order of control, mild, and severe AD mice group. Collectively, we found a significant difference in DRG gene expression profiles in comparisons of control and AD mice, as well as mild AD and severe AD mice. Furthermore, biomarkers such as Bdnf and Sting could be targetable to suppress the progression of AD and its symptoms.
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