Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China.
Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China; Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai, China.
J Dermatol Sci. 2020 May;98(2):109-118. doi: 10.1016/j.jdermsci.2020.03.006. Epub 2020 Apr 10.
Previous psoriasis studies have mostly focused on skin-related immunology, but the exact mechanisms remain elusive. Clinical evidence, such as higher morbidity among obese individuals and emotional factors, indicate that psoriasis is a complex systemic disease. High-throughput transcriptome analysis provides an effective method to comprehensively assess the disease.
The present study is aiming to understand transcriptome changes of clinical psoriasis skins and comprehensively assess the diseases using pathways analysis.
We performed transcriptome sequence of clinical psoriatic samples. Biological pathway analyses were conducted using differentially expressed RNAs, as well as identified competing endogenous RNAs (ceRNAs). qRT-PCR and histological immunofluorescence staining was conducted to verify the differentially expressed RNAs (DE_RNAs) and the three important enriched biological pathways.
Numerous DE_RNAs were identified between psoriasis patients and healthy people. Functional analysis indicated PPAR-fatty acids metabolism pathways, neural-hormone regulations, circadian entrainment were the three mostly appeared pathways. For PPAR-fatty acids metabolism pathways, the expression of seven randomly selected genes, including ACSBG1, ACOT2), CYP27A1, ELOVL3, FABP7, FADS2 and PPARG were all significantly decreased in psoriasis lesions. For neural-hormone regulation pathways, the expression of CFL1, EPHA2, HRAS were all significantly upregulated in psoriasis lesions. While the expression of four randomly selected genes from circadian entrainment pathways, including CRY2, PER3, NR1D1 and RORC were all significantly downregulated. Histological immunofluorescence staining of FADS2, EPHA2 and CRY2 were consistent with their genes' expressions.
Our results revealed transcriptome changes of psoriasis, and indicated three important pathways involved in psoriasis, including PPAR-fatty acids metabolism pathways, neural-hormone regulations, circadian entrainment.
先前的银屑病研究主要集中在皮肤相关免疫学方面，但确切机制仍难以捉摸。临床证据表明，肥胖人群和情绪因素等银屑病的发病率更高，表明其是一种复杂的系统性疾病。高通量转录组分析为全面评估疾病提供了一种有效的方法。
本研究旨在了解临床银屑病皮肤的转录组变化，并通过途径分析全面评估疾病。
我们对临床银屑病样本进行了转录组测序。使用差异表达 RNA 以及鉴定的竞争性内源性 RNA（ceRNA）进行生物途径分析。通过 qRT-PCR 和组织学免疫荧光染色来验证差异表达 RNA（DE_RNAs）和三个重要富集的生物途径。
在银屑病患者和健康人群之间鉴定出大量 DE_RNAs。功能分析表明，PPAR-脂肪酸代谢途径、神经-激素调节、昼夜节律同步是三个最常出现的途径。对于 PPAR-脂肪酸代谢途径，包括 ACSBG1、ACOT2、CYP27A1、ELOVL3、FABP7、FADS2 和 PPARG 在内的七个随机选择基因的表达在银屑病病变中均显著降低。对于神经-激素调节途径，CFL1、EPHA2、HRAS 的表达在银屑病病变中均显著上调。而昼夜节律同步途径中四个随机选择基因的表达，包括 CRY2、PER3、NR1D1 和 RORC，均显著下调。FADS2、EPHA2 和 CRY2 的组织学免疫荧光染色与它们的基因表达一致。
我们的结果揭示了银屑病的转录组变化，并指出了三个参与银屑病的重要途径，包括 PPAR-脂肪酸代谢途径、神经-激素调节、昼夜节律同步。
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