RPL22 Overexpression Promotes Psoriasis-Like Lesion by Inducing Keratinocytes Abnormal Biological Behavior

Abstract

BackgroundKeratinocytes of psoriasis have anti-apoptotic properties including delayed apoptosis process, accelerated proliferation metabolism and postponed differentiation process. However, the specific mechanism leading to the abnormal biological behavior of keratinocytes remains unclear.ObjectivesWe investigated the role of increased RPL22 expression in regulating the abnormal biological behavior of keratinocytes and the mechanism of regulation of RPL22 expression in skin lesions of psoriatic patients.MethodsWe examined clinical samples and utilized cytokine-induced cell and IMQ-treated mouse models. We determined the expression and functions of RPL22 in vitro and in vivo.ResultsWe showed that RPL22 expression was significantly increased in the skin lesions of psoriasis patients and IMQ-treated psoriatic-like mice. Such increased expression is attributed to hyperacetylation of histone H3K27 in the promoter region of RPL22. Interestingly, overexpression of RPL22 enhanced keratinocyte proliferation by increasing cyclinD1 expression and accelerated CD4+T cells recruitment via upregulating CXCL10 expression. Finally, we demonstrated that RPL22 overexpression promoted psoriasiform phenotypes in IMQ-induced mouse skins.ConclusionsThese findings suggested that RPL22 regulates keratinocytes abnormal biological behavior and contributes to the development of psoriatic phenotypes. Thus, RPL22 might be a novel potential molecular target for treatment of psoriasis.

Gene Profiling of a 3D Psoriatic Skin Model Enriched in T Cells: Downregulation of PTPRM Promotes Keratinocyte Proliferation through Excessive ERK1/2 Signaling

“…RSK is reportedly involved in numerous skin cancers by inducing cell cycle progression, cell proliferation and anchorage-independent cell transformation [ 52 ]. Since psoriatic keratinocytes are also characterized by excessive proliferation and anti-apoptotic properties, the inhibition of RSK in PS +T is consistent with the observed decrease in keratinocyte proliferation [ 53 , 54 ].…”

Transcriptomic meta-analysis characterizes molecular commonalities between psoriasis and obesity

“…The NES comparisons highlighted the inverted transcriptomic pro le of translational pathways and insulin secretion (Fig. 1e); translational activities induced by cell growth and differentiation, enhanced by the in ammatory pro le, are dysregulated during the hyperproliferation of keratinocytes in psoriasis [25,29] and the bioenergetic burden from the accumulated body fat in obesity, a discrepancy hypothesized to compile a homeostatic protective mechanism in MHO individuals [30,31]. Consistently, MHO patients exhibit an increased insulin secretion in comparison to lean [32] and insulin resistant [33] individuals, an expression pro le postulated to represent a transient state towards the exacerbation of metabolic complications and accompanied cardiovascular disorders [34].…”

Coptisine Alleviates Imiquimod-Induced Psoriasis-like Skin Lesions and Anxiety-like Behavior in Mice

“…Phosphorylated IKK could degrade IκB-α and liberate NF-κB from the complex with IκB-α, and triggering the nuclear translocation of NF-κB to regulate various downstream targets, including inflammatory molecules [52]. The high expression of NF-κB was reported in skin lesions from psoriasis patients, and the NF-κB signaling pathway was also highly activated in psoriatic keratinocytes [53,54]. The inhibition of NF-κB signaling is a potential therapeutic approach for psoriasis [55].…”