Abstract
Acne is the eighth most common disease worldwide. Disease burden of acne such as anxiety, reduced self-esteem, and facial scarring lowers the life quality of acne patients. Isotretinoin is the most potent treatment for moderate-severe acne. However, the adverse events of isotretinoin especially teratogenicity limit its use. This study aims at investigating the therapeutical mechanisms of isotretinoin using bioinformatics analysis. Differentially expressed genes (DEGs) were filtered from microarray datasets GSE10432, GSE10433, and GSE11792. Functional and pathway enrichment analyses of DEGs were performed. Protein–protein interaction (PPI) network and module analyses were also conducted based on DEGs. Using isotretinoin for 1 week, LCN2, PTGES, and GDF15 were upregulated and might mediate sebocytes apoptosis and thus decreased sebum production; CCL2 originated from activated TNF signaling pathway and S100A7 could be related with “acne-flare”. While treating with isotretinoin for 8 weeks, key genes were downregulated, including HMGCS1, HMGCR, FDFT1, MVD, IDI1, and FDPS, which may be associated with decreased sebum synthesis; HMGCS1, HMGCR, and FDFT1 also probably associated with apoptosis of sebocytes. There were only two common genes including ACSBG1 and BCAT2 which worked in both 1 week and 8 weeks and could associate with decreased sebum synthesis and apoptosis of sebocytes, respectively. These results indicate potential therapeutics and side effect mechanisms of isotretinoin in the acne treatment and provide a research direction to further investigate the therapeutic mechanism of isotretinoin and thus develop retinoid-like compounds with similar curative effect and without teratogenicity.
Highlights
Acne is the eighth most common disease worldwide with a morbidity of 94% according to the Global Burden of Disease Project [1]
There were consistently 0 upregulated (Figure 1(f)) and 2 downregulated (Figure 1(g)) genes, including ACSBG1 and BCAT2, among GSE10432 (SEB-1 sebocytes incubated with isotretinoin for 72 hours), GSE10433
The hub genes of the Protein– protein interaction (PPI) network of the common Differentially expressed genes (DEGs) in GSE10432 (SEB-1 sebocytes incubated with isotretinoin for 72 hours) and GSE10433 were upregulated
Summary
Acne is the eighth most common disease worldwide with a morbidity of 94% according to the Global Burden of Disease Project [1]. Treatments of acne include topical medication such as antibiotics, benzoyl peroxide, and retinoids; and systemic medication such as isotretinoin, tetracyclines, and spironolactone [3]; as well as other miscellaneous therapies including chemical peels, intralesional injection of triamcinolone acetonide, and laser and light therapies [4]. Isotretinoin is the first line and the most potent treatment for moderate-severe acne [4, 5]. The adverse events of isotretinoin include elevated liver enzymes [6] and serum lipids, xerosis, cheilitis, eye dryness, irritation and conjunctival injection, fatigue, depressed mood, arthralgia, and teratogenicity [7]. Considering the therapeutic effect and adverse events, there is an emerging need to explore the mechanism of acne treatment with isotretinoin, and develop retinoid-like compounds with similar curative effect and without teratogenicity
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