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• W4366185772 abstract "The circadian clock is a group of oscillatory auto-regulatory transcription factors which give rise to circadian rhythms of gene expression and enable alignment of cellular function with the environment. Human skin has a robust clock and psoriasis is influenced by circadian rhythms. However, it remains unknown whether circadian clock genes are dysregulated in lesional skin. We analyzed timestamped transcriptomic data from the PSORT (Psoriasis Stratification to Optimize Relevant Therapy) consortium to compare differentially expressed genes between the morning and afternoon (c-DEGs; q.value <0.05 and fold change ≥1.5) between lesional(LS) and non-lesional(NLS) skin. Across discovery and replication cohorts, 113 patients with psoriasis provided baseline LS and NLS biopsies. Biopsies taken before 10:00 AM (21 LS, 21 NLS) or after 2:00 PM (20 LS, 20 NLS) were selected for analysis. In NLS, there were 65 c-DEGs. 38% of these (25/65) were recognized rhythmic genes described in other tissues and 40% (26/65) were not previously time of day associated in any tissue. Notably, systems analysis, using Ingenuity Pathway Analysis(IPA), identified circadian rhythm as the top pathway. There was decreased expression of core circadian clock genes CIART, PER1 and NR1D1 and increased expression of antiphase clock genes ARNTL and CRY1 in the afternoon compared with the morning. In contrast, in LS there were only five c-DEGs, with one novel c-DEG in skin. Expression of CIART, PER1 and NR1D1 was decreased with CRY1 increased in the afternoon compared with the morning, but unlike NLS, ARNTL was not significantly increased. Correlation matrices showed that NLS closely resembled that of normal healthy skin, whereas in LS circadian rhythms appeared to be disrupted (Mantel Z-score 36.9 for NLS, 27.4 for LS vs reference data). These findings provide evidence that whilst circadian rhythms are maintained in non-lesional psoriasis skin, in lesional skin the circadian clock is dysregulated." @default.
• W4366185772 created "2023-04-19" @default.
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• W4366185772 date "2023-05-01" @default.
• W4366185772 modified "2023-09-28" @default.
• W4366185772 title "1328 Dysregulation of circadian clocks in psoriasis" @default.
• W4366185772 doi "https://doi.org/10.1016/j.jid.2023.03.1344" @default.
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