Department of Pathophysiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan.
Department of Dermatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan.
Biomolecules. 2022 Dec 6;12(12):1822. doi: 10.3390/biom12121822.
While topical corticosteroid (TCS) treatment is widely used for many skin diseases, it can trigger adverse side effects, and some of such effects can last for a long time after stopping the treatment. However, molecular changes induced by TCS treatment remain largely unexplored, although transient changes in histology and some major ECM components have been documented. Here, we investigated transcriptomic and proteomic changes induced by fluocinolone acetonide (FA) treatment in the mouse skin by conducting RNA-Seq and quantitative proteomics. Chronic FA treatment affected the expression of 4229 genes, where downregulated genes were involved in cell-cycle progression and ECM organization, and upregulated genes were involved in lipid metabolism. The effects of FA on transcriptome and histology of the skin largely returned to normal by two weeks after the treatment. Only a fraction of transcriptomic changes were reflected by proteomic changes, and the expression of 46 proteins was affected one day after chronic FA treatment. A comparable number of proteins were differentially expressed between control and FA-treated skin samples even at 15 and 30 days after stopping chronic FA treatment. Interestingly, proteins affected during and after chronic FA treatment were largely different. Our results provide fundamental information of molecular changes induced by FA treatment in the skin.
虽然局部皮质类固醇(TCS)治疗被广泛用于许多皮肤病,但它会引发不良反应,其中一些不良反应在停止治疗后会持续很长时间。然而,尽管已经记录了组织学和一些主要 ECM 成分的短暂变化,但 TCS 治疗引起的分子变化在很大程度上仍未得到探索。在这里,我们通过进行 RNA-Seq 和定量蛋白质组学研究,调查了氟轻松丙酮(FA)治疗在小鼠皮肤中引起的转录组和蛋白质组变化。慢性 FA 治疗影响了 4229 个基因的表达,下调的基因参与细胞周期进展和 ECM 组织,上调的基因参与脂质代谢。FA 对皮肤的转录组和组织学的影响在治疗后两周内基本恢复正常。只有一部分转录组变化反映在蛋白质组变化中,46 种蛋白质的表达在慢性 FA 治疗后一天受到影响。即使在停止慢性 FA 治疗 15 天和 30 天后,对照和 FA 处理的皮肤样本之间也有相当数量的蛋白质表达差异。有趣的是,在慢性 FA 治疗期间和之后受影响的蛋白质在很大程度上是不同的。我们的研究结果提供了 FA 治疗在皮肤中引起的分子变化的基本信息。