Histone modifications associated with biological drug response in moderate‐to‐severe psoriasis

Ovejero‐Benito, María C.; Reolid, Alejandra; Sánchez‐Jiménez, Patricia; Saiz‐Rodríguez, Miriam; Muñoz‐Aceituno, Ester; Llamas‐Velasco, M.; Martı́n-Vı́lchez, Samuel; Cabaleiro, Teresa; Román, Manuel; Ochoa, Dolores; Daudén, E.; Abad‐Santos, Francisco

doi:10.1111/exd.13790

Cited by 56 publications

(42 citation statements)

References 49 publications

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“…Moreover, after introducing biological treatment there were no significant changes in histone modification. Nevertheless, a significant difference in H3K27 alternations was found between responders and non-responders to the biological agent after three months of treatment [36].…”

Section: State Of Knowledgementioning

confidence: 84%

Environmental risk factors and epigenetic alternations in psoriasis

Roszkiewicz¹,

Dopytalska²,

Szymańska³

et al. 2020

Ann Agric Environ Med.

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Introduction and objective. Psoriasis isa quite common, chronic and immune-mediated skin disorder. The prevalence of psoriasis differs in various countries, but it is said to affect 2% of the world's population in general. Psoriasis has many different clinical features but all lesions have the same characteristic: erythema, thickening and scale, although other clinical features are also connected, such as psoriatic arthritis, obesity and metabolic syndrome. All of these may lead to conditions impairing the quality of life. This review is an attempt to summarize recent data regarding environmental factors, together with epigenetic markers and processes playing an important role in psoriasis. State of knowledge. Many different environmental factors play a role in genetically predisposed patients. This is causes epigenetic alternations which may be a linking part in the whole process. Many studies have indicated a connection between psoriasis and various genes and antigens. The presence of HLA-Cw6 is common as well a strong link between its presence and the onset of psoriasis being observed. The main alternations are DNA methylation, histone's modifications and the role of microRNA. Excessive reaction is usually not present without a triggering factor. Environmental factors are mostly rated, such as drugs, life style and habits (smoking, alcohol), diet, physical trauma (skin injury provoking Koebner phenomenon), stress, microorganism and infections. Conclusions. The correlation between pathogenesis of psoriasis and environmental risk factors, together with epigenetic alternations still require more investigation. Education about diet habits, nutrition, weight loss and healthy lifestyle seems to be important during the treatment of psoriasis.

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Section: State Of Knowledgementioning

confidence: 84%

Environmental risk factors and epigenetic alternations in psoriasis

Roszkiewicz¹,

Dopytalska²,

Szymańska³

et al. 2020

Ann Agric Environ Med.

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“…They examined changes in the level of histone modification in PBMC of psoriasis patients before and after treatment with biological agents. They found that although H3K27 methylation in PBMC of patients was not significantly different from healthy subjects before treatment, H3K27 levels were significantly elevated in biologic responders after 3 months of treatment compared to nonresponders 30 . In another study, researchers found that EZH2 was significantly increased in psoriasis, but there was no significant difference in H3K27me3 26 .…”

Section: Discussionmentioning

confidence: 98%

EZH2-dependent epigenetic modulation of histone H3 lysine-27 contributes to psoriasis by promoting keratinocyte proliferation

Zhang

Yang

et al. 2020

Cell Death Dis

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Psoriasis is characterized by keratinocyte hyperproliferation. While significant progress has been made in understanding the molecular mechanism regulating the proliferation of keratinocytes, little is known about the epigenetic factors that control this process. EZH2 and EZH2 mediated trimethylation of histone H3 lysine 27 (H3K27me3) was previously shown ectopically expressed in carcinoma and mediated proliferation, thereby we sought to clarify the role of EZH2–H3K27me3 in the proliferation of psoriatic keratinocyte. Interestingly, we found that EZH2 and H3K27me3 were both overexpressed in the epidermis of psoriatic lesional skin compared to normal skin. In vitro, the expression of EZH2 and H3K27me3 was stimulated in human keratinocytes treated with mixture of psoriasis-related cytokines pool (TNF-α, IFN-γ, IL-17A, and IL-22). Knockdown of EZH2 significantly reduced keratinocyte proliferative activity. Results from mRNA microarray analysis suggested that Kallikrein-8 (KLK8) might be the target gene of EZH2 in psoriatic keratinocytes. Overexpression or knockdown KLK8 could partially reverse the abnormal proliferation of keratinocytes caused by knockdown or overexpression of EZH2. In vivo, the inhibitor of EZH2, GSK126 could ameliorate the imiquimod-induced psoriasiform lesion. These results suggest that EZH2 might be a therapeutic target for the treatment of psoriasis.

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“…Ovejero-Benito et al [ 71 ] studied epigenetic changes in responders and non-responders to biological drugs (ustekinumab, secukinumab, adalimumab, ixekizumab). Significant changes in methylated lysine 27 in histone 27 (H3K27) and methylated lysine in histone 3 (H3K4) in patients with psoriatic arthritis were found between responders and non-responders.…”

Section: Histone Modification In Psoriasismentioning

confidence: 99%

Pathogenesis of psoriasis in the “omic” era. Part II. Genetic, genomic and epigenetic changes in psoriasis

Nedoszytko¹,

Szczerkowska‐Dobosz²,

Stawczyk-Macieja³

et al. 2020

pdia

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Psoriasis is a multifactorial disease in which genetic, environmental and epigenetic factors regulating gene expression play a key role. In the “genomic era”, genome-wide association studies together with target genotyping platforms performed in different ethnic populations have found more than 50 genetic susceptible markers associated with the risk of psoriasis which have been identified so far. Up till now, the strongest association with the risk of the disease has been proved for HLA-C*06 gene. The majority of other psoriasis risk SNPs are situated near the genes encoding molecules involved in adaptive and innate immunity, and skin barrier function. Many contemporary studies indicate that the epigenetic changes: histone modification, promoter methylations, long non-coding and micro-RNA hyperexpression are considered as factors contributing to psoriasis pathogenesis as they regulate abnormal keratinocyte differentiation and proliferation, aberrant keratinocytes – inflammatory cells communication, neoangiogenesis and chronic inflammation. The circulating miRNAs detected in the blood may become specific markers in the diagnosis, prognosis and response to the treatment of the disease. The inhibition of expression in selected miRNAs may be a new promising therapy option for patients with psoriasis.

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Histone modifications associated with biological drug response in moderate‐to‐severe psoriasis

Cited by 56 publications

References 49 publications

Environmental risk factors and epigenetic alternations in psoriasis

Environmental risk factors and epigenetic alternations in psoriasis

EZH2-dependent epigenetic modulation of histone H3 lysine-27 contributes to psoriasis by promoting keratinocyte proliferation

Pathogenesis of psoriasis in the “omic” era. Part II. Genetic, genomic and epigenetic changes in psoriasis

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