Tang Yi, Li Ma, Su Yixin, Du Yue, Wu Xia, Chen Xianzhen, Song Yinjing, Lai Lihua, Cheng Hao
Department of Dermatology and Venereology, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China; Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Department of Dermatology and Venereology, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China.
Life Sci. 2023 Mar 15;317:121474. doi: 10.1016/j.lfs.2023.121474. Epub 2023 Feb 4.
Atopic dermatitis (AD) is a common chronic inflammatory skin disorder that affects up to 20 % of children and 10 % of adults worldwide; however, the exact molecular mechanisms remain largely unknown.
In this study, we used integrated transcriptomic and metabolomic analyses to study the potential mechanisms of 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like skin lesions.
We found that DNCB induced AD-like skin lesions, including phenotypical and histomorphological alterations and transcriptional and metabolic alterations in mice. A total of 3413 differentially expressed metabolites were detected between DNCB-induced AD-like mice and healthy controls, which includes metabolites in taurine and hypotaurine metabolism, phenylalanine metabolism, biosynthesis of unsaturated fatty acids, tryptophan metabolism, arachidonic acid metabolism, pantothenate and CoA biosynthesis, pyrimidine metabolism, and glycerophospholipid metabolism pathways. Furthermore, the differentially expressed genes associated (DEGs) with these metabolic pathways were analyzed using RNA sequencing (RNA-seq), and we found that the expression of pyrimidine metabolism-associated genes was significantly increased. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the glycolysis/gluconeogenesis, glucagon signaling pathway and pentose phosphate pathway-associated metabolic genes were dramatically altered.
Our results explain the possible mechanism of AD at the gene and metabolite levels and provide potential targets for the development of clinical drugs for AD.
特应性皮炎（AD）是一种常见的慢性炎症性皮肤病，全球高达20%的儿童和10%的成年人受其影响；然而，确切的分子机制仍 largely未知。
在本研究中，我们使用综合转录组学和代谢组学分析来研究1-氯-2,4-二硝基苯（DNCB）诱导的类AD皮肤病变的潜在机制。
我们发现DNCB诱导了类AD皮肤病变，包括小鼠的表型和组织形态学改变以及转录和代谢改变。在DNCB诱导的类AD小鼠和健康对照之间共检测到3413种差异表达的代谢物，其中包括牛磺酸和亚牛磺酸代谢、苯丙氨酸代谢、不饱和脂肪酸生物合成、色氨酸代谢、花生四烯酸代谢、泛酸和辅酶A生物合成、嘧啶代谢以及甘油磷脂代谢途径中的代谢物。此外，使用RNA测序（RNA-seq）分析了与这些代谢途径相关的差异表达基因（DEGs），我们发现嘧啶代谢相关基因的表达显著增加。京都基因与基因组百科全书（KEGG）途径分析表明，糖酵解/糖异生、胰高血糖素信号通路和磷酸戊糖途径相关的代谢基因发生了显著改变。
我们的结果在基因和代谢物水平上解释了AD的可能机制，并为AD临床药物的开发提供了潜在靶点。
