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Characterization of Transcriptomic and Proteomic Changes in the Skin after Chronic Fluocinolone Acetonide Treatment
Yongsu Choi1,2, Masaki Takasugi1, Kazuaki Takemura1
1Department of Pathophysiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan.
Abstract:
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.
Insights
Topical corticosteroid (TCS) treatment causes molecular skin changes, primarily affecting lipid metabolism and cell cycle. While skin histology recovers post-treatment, proteomic alterations persist long-term.
Area of Science:
- Dermatology
- Molecular Biology
- Genomics
Background:
- Topical corticosteroids (TCS) are common treatments for skin conditions.
- TCS can cause persistent adverse side effects.
- Molecular mechanisms underlying TCS effects are not fully understood.
Purpose of the Study:
- To investigate transcriptomic and proteomic changes in mouse skin induced by fluocinolone acetonide (FA).
- To understand the duration and nature of molecular alterations following chronic FA treatment.
Main Methods:
- RNA-sequencing (RNA-Seq) for transcriptomic analysis.
- Quantitative proteomics for proteomic analysis.
- Analysis of skin samples during and after chronic FA treatment.
Main Results:
- Chronic FA treatment altered 4229 genes, impacting cell-cycle progression, ECM organization, and lipid metabolism.
- Transcriptomic and histologic changes largely normalized within two weeks post-treatment.
- Proteomic changes differed from transcriptomic ones, with 46 proteins affected acutely and persistent differential protein expression observed 15-30 days after treatment cessation.
Conclusions:
- FA treatment induces significant, yet largely reversible, transcriptomic and histologic changes in the skin.
- Proteomic alterations during and after FA treatment are distinct and can persist long after cessation.
- This study provides crucial molecular insights into FA's effects on skin.
