Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy,
Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy.
Cell Physiol Biochem. 2024 Aug 20;58(4):404-417. doi: 10.33594/000000720.
BACKGROUND/AIMS: Aquaporin-3 (AQP3) is an aquaglyceroporin and peroxiporin that plays a crucial role in skin barrier homeostasis. Dysregulated AQP3 expression has been observed in different inflammatory skin conditions. Hidradenitis Suppurativa (HS) is an autoinflammatory keratinization disease that typically appears between 10 and 21 years of age, characterized by alteration of skin barrier homeostasis.
To evaluate the role of AQP3 in the development of HS, we performed real-time PCR and Western blot to analyze gene and protein levels in human keratinocyte cell lines knock-out (KO) for and genes, simulating genetic-associated HS. Additionally, we investigated the impact of Glyceryl Glucoside (GG) on biological processes by performing MTT, scratch, proliferation assays and proteome studies.
We detected a significant decrease of the levels of AQP3 gene and protein in KO cell lines. GG effectively elevated the levels of mRNA and protein, significantly decreased the hyperproliferation rate, and enhanced cell migration in our model of genetic Hidradenitis Suppurativa. Pathway enrichment analysis further confirmed GG's role in the migration and proliferation pathways of keratinocytes.
Our results suggest that AQP3 may act as a new novel actor in HS etio-pathogenesis, and GG could be further explored as potential treatment option for managing HS in patients.
背景/目的：水通道蛋白 3（AQP3）是一种水甘油通道蛋白和过氧化物通道蛋白，在皮肤屏障稳态中起着至关重要的作用。在不同的炎症性皮肤疾病中观察到 AQP3 表达失调。化脓性汗腺炎（HS）是一种自身炎症性角化病，通常在 10 至 21 岁之间出现，其特征是皮肤屏障稳态发生改变。
为了评估 AQP3 在 HS 发展中的作用，我们通过实时 PCR 和 Western blot 分析模拟遗传相关 HS 的基因和蛋白水平，在敲除 和 基因的人角质形成细胞系中进行检测。此外，我们通过 MTT、划痕、增殖试验和蛋白质组学研究研究了 Glyceryl Glucoside（GG）对生物过程的影响。
我们在 KO 细胞系中检测到 AQP3 基因和蛋白水平显著降低。GG 可有效上调 mRNA 和蛋白水平，显著降低增殖率，并增强我们遗传 HS 模型中的细胞迁移。通路富集分析进一步证实 GG 在角质形成细胞的迁移和增殖途径中的作用。
我们的结果表明 AQP3 可能是 HS 发病机制中的一个新的新型作用因子，并且 GG 可以进一步探索作为治疗 HS 患者的潜在治疗选择。
