Expression Patterns of Clock Gene mRNAs and Clock Proteins in Human Psoriatic Skin Samples

Abstract

Psoriasis is a systemic inflammatory skin disorder that can be associated with sleep disturbance and negatively influence the daily rhythm. The link between the pathomechanism of psoriasis and the circadian rhythm has been suggested by several previous studies. However, there are insufficient data on altered clock mechanisms in psoriasis to prove these theories. Therefore, we investigated the expression of the core clock genes in human psoriatic lesional and non-lesional skin and in human adult low calcium temperature (HaCaT) keratinocytes after stimulation with pro-inflammatory cytokines. Furthermore, we examined the clock proteins in skin biopsies from psoriatic patients by immunohistochemistry. We found that the clock gene transcripts were elevated in psoriatic lesions, especially in non-lesional psoriatic areas, except for rev-erbα, which was consistently downregulated in the psoriatic samples. In addition, the REV-ERBα protein showed a different epidermal distribution in non-lesional skin than in healthy skin. In cytokine-treated HaCaT cells, changes in the amplitude of the bmal1, cry1, rev-erbα and per1 mRNA oscillation were observed, especially after TNFα stimulation. In conclusion, in our study a perturbation of clock gene transcripts was observed in uninvolved and lesional psoriatic areas compared to healthy skin. These alterations may serve as therapeutic targets and facilitate the development of chronotherapeutic strategies in the future.

LiangxueJiedu Formula improves psoriatic dermatitis by regulating the circadian clock to inhibit IL-17-producing Th17 and γδT cells

“…Clock genes and the cell cycle regulators can in turn affect the up-regulation of their expression and thus participate in abnormal cell proliferation. After Per2 gene knockout, the expression of CLOCK/BMAL1 gene may contribute to the hyperproliferation of psoriasis [30]. The coordination of the cell cycle in epidermal stem cells by core components of the molecular clock indicating that circadian clock might contribute to the hyperproliferation of keratinocytes in the basal layer of psoriatic plaques [13,31].…”

Regular Late Bedtime Significantly Affects the Skin Physiological Characteristics and Skin Bacterial Microbiome

“…30 , 38 Indeed, recent studies have also linked the circadian clock to psoriasis, sensitive skin and atopic dermatitis. 39–42 Moreover, it was reported that poor sleep quality deregulated the immune system and impaired the integrity of collagen fibers, 43 , 44 which might another reason for the reduction of skin elasticity and firmness. Therefore, we speculated that the significant reduction of skin firmness and elasticity in the late bedtime group was probably also linked with altered circadian rhythms caused by regular late bedtime.…”

Potential effects of shift work on skin autoimmune diseases

“…To unravel the link between the circadian clock and psoriasis, a transcriptomic study showed a downregulation of CRY1/2, REVERBA, CLOCK, BMAL1 and RORA/C in keratinocytes from psoriatic lesions ( 269 ). A recent study found changes in core clock genes and clock proteins in non-lesional and lesional human skin samples in psoriasis ( 270 ). In a mouse model, imiquimod-induced psoriasis-like dermatitis was ameliorated in mice with a loss of function mutation in the Clock gene compared to wild-type mice.…”