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咪喹莫特诱导的急性和慢性小鼠银屑病模型皮肤特征的比较分析

Comparative analysis of cutaneous features of psoriasis in acute and chronic imiquimod-induced mouse models.

作者信息

Fraillon Emma, Jégou Jean-François, Rabeony Hanitriniaina, Lecron Jean-Claude, Lebonvallet Nicolas, Marie-Joseph Emilie, Josset-Lamaugarny Audrey, Aimond Géraldine, Misery Laurent, Morel Franck, Chevalier Fabien P, Fromy Bérengère

机构信息

Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, CNRS UMR5305, Université Claude Bernard Lyon 1, Lyon, France.

Laboratoire Inflammation, Tissus Épithéliaux et Cytokines, Université de Poitiers UR15560, Poitiers, France.

出版信息

Sci Rep. 2025 Jul 23;15(1):26834. doi: 10.1038/s41598-025-12111-6.

DOI:10.1038/s41598-025-12111-6
PMID:40702143
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12287311/
Abstract

Psoriasis is a chronic inflammatory skin disorder influenced by genetic and environmental factors. The imiquimod (IMQ)-induced mouse model is widely used to study psoriasis-like skin inflammation. However, its current use is largely limited to short treatment periods. Therefore, this model predominantly reflects acute inflammation and is limited in its capacity to capture the chronic nature of psoriasis. To date, little attention has been given to the extension of IMQ treatment duration to study the characteristics of sustained inflammation. This study aimed to provide the first direct comparison between short-term (ST, 4 days) and long-term (LT, 9 weeks) IMQ treatments on cutaneous histological, molecular and functional psoriasis features and to assess their similarity with human psoriasis. Both models demonstrated similar global severity, but with distinct features: ST-IMQ treatment led to increased epidermal hyperplasia and impaired skin barrier function, while LT-IMQ treatment was associated with greater desquamation and impaired suprabasal differentiation. Dermal mechanical properties and endothelial dysfunction were similar between the two models. Gene expression analysis revealed differentially expressed psoriasis-related markers between ST- and LT-IMQ treatments, with both models showing similarities to human psoriasis. These findings offer critical insights into how acute and chronic models can be tailored to study specific psoriasis features.

摘要

银屑病是一种受遗传和环境因素影响的慢性炎症性皮肤病。咪喹莫特(IMQ)诱导的小鼠模型被广泛用于研究银屑病样皮肤炎症。然而,目前其应用主要局限于短期治疗。因此,该模型主要反映急性炎症,在捕捉银屑病慢性特征方面能力有限。迄今为止,很少有人关注延长IMQ治疗时间以研究持续炎症的特征。本研究旨在首次直接比较短期(ST,4天)和长期(LT,9周)IMQ治疗对皮肤组织学、分子和功能性银屑病特征的影响,并评估它们与人类银屑病的相似性。两种模型均表现出相似的整体严重程度,但具有不同特征:ST-IMQ治疗导致表皮增生增加和皮肤屏障功能受损,而LT-IMQ治疗则与更大程度的脱屑和基底上层分化受损有关。两种模型之间的皮肤力学性能和内皮功能障碍相似。基因表达分析显示ST-和LT-IMQ治疗之间存在差异表达的银屑病相关标志物,两种模型均显示出与人类银屑病的相似性。这些发现为如何定制急性和慢性模型以研究特定的银屑病特征提供了关键见解。

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Comparative analysis of cutaneous features of psoriasis in acute and chronic imiquimod-induced mouse models.咪喹莫特诱导的急性和慢性小鼠银屑病模型皮肤特征的比较分析
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本文引用的文献

1
Extending the IMQ Model: Deep Characterization of the Human TLR7 Response for Early Drug Development.扩展IMQ模型:用于早期药物开发的人类TLR7反应的深度表征
Inflammation. 2024 Aug 26. doi: 10.1007/s10753-024-02127-x.
2
Epidermal Barrier Parameters in Psoriasis: Implications in Assessing Disease Severity.银屑病中的表皮屏障参数:对评估疾病严重程度的意义。
J Pers Med. 2024 Jul 5;14(7):728. doi: 10.3390/jpm14070728.
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Factor XII and prekallikrein promote microvascular inflammation and psoriasis in mice.因子 XII 和激肽原酶促进小鼠微血管炎症和银屑病。
Br J Pharmacol. 2024 Oct;181(19):3760-3778. doi: 10.1111/bph.16428. Epub 2024 Jun 13.
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Skin Cell and Tissue Responses to Cross-Linked Hyaluronic Acid in Low-Grade Inflammatory Conditions.皮肤细胞和组织在低度炎症条件下对交联透明质酸的反应。
Int J Inflam. 2023 Aug 26;2023:3001080. doi: 10.1155/2023/3001080. eCollection 2023.
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Single cell and spatial sequencing define processes by which keratinocytes and fibroblasts amplify inflammatory responses in psoriasis.单细胞和空间测序定义了角质形成细胞和成纤维细胞在银屑病中放大炎症反应的过程。
Nat Commun. 2023 Jun 12;14(1):3455. doi: 10.1038/s41467-023-39020-4.
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Epidemiology of Psoriasis and Comorbid Diseases: A Narrative Review.银屑病的流行病学和合并症:一篇叙述性综述。
Front Immunol. 2022 Jun 10;13:880201. doi: 10.3389/fimmu.2022.880201. eCollection 2022.
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Mouse Models of Psoriasis: A Comprehensive Review.银屑病小鼠模型:全面综述。
J Invest Dermatol. 2022 Mar;142(3 Pt B):884-897. doi: 10.1016/j.jid.2021.06.019. Epub 2021 Dec 23.
8
Keratinocyte differentiation and proteolytic pathways in skin (patho) physiology.皮肤(病理)生理学中的角质形成细胞分化和蛋白水解途径。
Int J Dev Biol. 2022;66(1-2-3):269-275. doi: 10.1387/ijdb.210161gs.
9
Extracellular matrix alterations in the skin of patients affected by psoriasis.银屑病患者皮肤细胞外基质的改变。
BMC Mol Cell Biol. 2021 Oct 29;22(1):55. doi: 10.1186/s12860-021-00395-1.
10
2,4-Dimethoxy-6-Methylbenzene-1,3-diol, a Benzenoid From , Mitigates Psoriasiform Inflammation by Suppressing MAPK/NF-κB Phosphorylation and GDAP1L1/Drp1 Translocation.2,4-二甲氧基-6-甲基苯-1,3-二醇,一种来自 的苯并呋喃类化合物,通过抑制 MAPK/NF-κB 磷酸化和 GDAP1L1/Drp1 易位来减轻银屑病样炎症。
Front Immunol. 2021 May 14;12:664425. doi: 10.3389/fimmu.2021.664425. eCollection 2021.