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利用 LC-MS/MS 对病变和正常外观的银屑病皮肤进行分析,揭示了蛋白质代谢和 RNA 处理的显著变化。

LC-MS/MS analysis of lesional and normally looking psoriatic skin reveals significant changes in protein metabolism and RNA processing.

机构信息

I. Mechnikov Research Institute for Vaccines and Sera RAMS, Moscow, Russian Federation.

Centre of Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russian Federation.

出版信息

PLoS One. 2021 May 26;16(5):e0240956. doi: 10.1371/journal.pone.0240956. eCollection 2021.

Abstract

BACKGROUND

Plaque psoriasis is a chronic autoimmune disorder characterized by the development of red scaly plaques. To date psoriasis lesional skin transcriptome has been extensively studied, whereas only few proteomic studies of psoriatic skin are available.

AIM

The aim of this study was to compare protein expression patterns of lesional and normally looking skin of psoriasis patients with skin of the healthy volunteers, reveal differentially expressed proteins and identify changes in cell metabolism caused by the disease.

METHODS

Skin samples of normally looking and lesional skin donated by psoriasis patients (n = 5) and samples of healthy skin donated by volunteers (n = 5) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After protein identification and data processing, the set of differentially expressed proteins was subjected to protein ontology analysis to characterize changes in biological processes, cell components and molecular functions in the patients' skin compared to skin of the healthy volunteers. The expression of selected differentially expressed proteins was validated by ELISA and immunohistochemistry.

RESULTS

The performed analysis identified 405 and 59 differentially expressed proteins in lesional and normally looking psoriatic skin compared to healthy control. In normally looking skin of the patients, we discovered decreased expression of KNG1, APOE, HRG, THBS1 and PLG. Presumably, these changes were needed to protect the epidermis from spontaneous activation of kallikrein-kinin system and delay the following development of inflammatory response. In lesional skin, we identified several large groups of proteins with coordinated expression. Mainly, these proteins were involved in different aspects of protein and RNA metabolism, namely ATP synthesis and consumption; intracellular trafficking of membrane-bound vesicles, pre-RNA processing, translation, chaperoning and degradation in proteasomes/immunoproteasomes.

CONCLUSION

Our findings explain the molecular basis of metabolic changes caused by disease in skin lesions, such as faster cell turnover and higher metabolic rate. They also indicate on downregulation of kallikrein-kinin system in normally looking skin of the patients that would be needed to delay exacerbation of the disease. Data are available via ProteomeXchange with identifier PXD021673.

摘要

背景

斑块状银屑病是一种慢性自身免疫性疾病,其特征为红色鳞屑斑块的发展。迄今为止,银屑病皮损的转录组已得到广泛研究,而仅有少数银屑病皮肤的蛋白质组学研究可用。

目的

本研究旨在比较银屑病患者皮损和正常皮肤与健康志愿者皮肤的蛋白质表达模式,揭示差异表达的蛋白质,并确定疾病引起的细胞代谢变化。

方法

对 5 例银屑病患者的正常皮肤和皮损皮肤样本(n=5)和 5 例志愿者的健康皮肤样本(n=5)进行了液相色谱-串联质谱(LC-MS/MS)分析。在蛋白质鉴定和数据处理后,对差异表达蛋白进行蛋白质本体分析,以描述与健康志愿者皮肤相比,患者皮肤中生物过程、细胞成分和分子功能的变化。通过 ELISA 和免疫组织化学验证了所选差异表达蛋白的表达。

结果

与健康对照组相比,皮损和正常银屑病皮肤分别鉴定出 405 种和 59 种差异表达蛋白。在患者的正常皮肤中,我们发现 KNG1、APOE、HRG、THBS1 和 PLG 的表达减少。推测这些变化是为了保护表皮免受激肽释放酶-激肽系统的自发激活,并延迟随后的炎症反应的发展。在皮损皮肤中,我们鉴定出几个具有协调表达的蛋白质大组。主要是,这些蛋白质参与了蛋白质和 RNA 代谢的不同方面,即 ATP 的合成和消耗;膜结合囊泡的细胞内运输、前 RNA 加工、翻译、伴侣和蛋白酶体/免疫蛋白酶体中的降解。

结论

我们的研究结果解释了皮肤病变中由疾病引起的代谢变化的分子基础,例如更快的细胞更替和更高的代谢率。它们还表明,患者正常皮肤中激肽释放酶-激肽系统的下调,以延迟疾病的恶化。数据可通过 ProteomeXchange 以标识符 PXD021673 获得。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0e6/8153457/5f6fe6fede6a/pone.0240956.g001.jpg

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