Using the AP1 Transcription Factor FOSL1 to Assess the Exacerbation of Psoriasis.

IF 2.2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Current molecular medicine Pub Date : 2025-01-17 DOI:10.2174/0115665240343441241231102305
Vladimir Sobolev, Anna Soboleva, Ksenia Katkova, Elena Denisova, Olga Zhukova, Nikolay Potekaev, Luiza Sakanyia, Irina Korsunskaya, Alexandre Mezentsev
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Abstract

Background: The transcription factor AP1 plays a crucial role in the proliferation, apoptosis, and terminal differentiation of epidermal keratinocytes.

Objective: This study aimed to clarify whether the subunit of AP1, FOSL1 protein, can be used to assess the exacerbation of psoriasis by evaluating its changes in protein and mRNA levels in cultured epidermal keratinocytes and skin specimens of the patients prescribed with bathwater PUVA (Psoralen and UVA) therapy. This study aimed to investigate FOSL1, a subunit of the transcription factor AP-1, as a potential biomarker for psoriasis by examining its protein and mRNA expression in skin specimens from patients undergoing bathwater PUVA (Psoralen and UVA) therapy and cultured epidermal keratinocytes.

Methods: The distribution of FOSL1 in patients' skin was explored by immunohistochemistry. Changes in gene and protein expression were quantitatively assessed by qPCR and ELISA, respectively.

Results: Immunohistochemistry analysis revealed that FOSL1 accumulated in lesional skin. The expression of FOSL1 significantly increased during disease flare-ups but decreased following the treatment with bathwater PUVA therapy. Furthermore, silencing FOSL1 led to a marked reduction in the expression of ten FOSL1 target genes associated with the disease.

Conclusion: Our study suggests that FOSL1 shows potential as a biomarker for psoriasis. This is supported by two key findings: first, the expression of FOSL1 correlates with disease activity, and second, its expression is linked to changes in the expression of genes previously implicated in the pathogenesis of psoriasis, namely MMP1, MMP9, IVL, CCNA2, CCL2, HMOX1, PLAU, PLAUR, and THBD.

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应用AP1转录因子FOSL1评估银屑病恶化。
背景:转录因子AP1在表皮角质形成细胞的增殖、凋亡和终末分化中起着至关重要的作用。目的:本研究旨在通过评估洗浴水PUVA(补骨脂素和UVA)治疗患者表皮角质形成细胞和皮肤标本中AP1亚基FOSL1蛋白的蛋白和mRNA水平的变化,阐明AP1亚基FOSL1蛋白是否可以用来评估银屑病的恶化。本研究旨在通过检测接受沐浴水PUVA(补骨脂素和UVA)治疗的患者皮肤标本和培养的表皮角质形成细胞中FOSL1的蛋白和mRNA表达,研究FOSL1是转录因子AP-1的一个亚基,作为银屑病的潜在生物标志物。方法:采用免疫组化方法观察FOSL1在患者皮肤中的分布。分别用qPCR和ELISA定量检测基因和蛋白表达的变化。结果:免疫组化分析显示FOSL1在病变皮肤中积累。FOSL1的表达在疾病发作期间显著增加,但在沐浴水PUVA治疗后下降。此外,沉默FOSL1导致与该疾病相关的十个FOSL1靶基因的表达显著降低。结论:我们的研究表明FOSL1具有作为银屑病生物标志物的潜力。这得到了两个关键发现的支持:首先,FOSL1的表达与疾病活动性相关,其次,它的表达与先前与银屑病发病机制相关的基因表达变化有关,即MMP1、MMP9、IVL、CCNA2、CCL2、HMOX1、PLAU、PLAUR和THBD。
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来源期刊
Current molecular medicine
Current molecular medicine 医学-医学:研究与实验
CiteScore
5.00
自引率
4.00%
发文量
141
审稿时长
4-8 weeks
期刊介绍: Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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