Hyperproliferative Skin Diseases Research Articles

Towards the Use of Lichens as a Source of Bioactive Substances for Topical Applications.

The increasing incidence of dermatological diseases prompts the search for new natural methods of treatments, and lichens, with their special symbiotic structure, are a little-known and promising source of biologically active substances. Seven lichen species, Cladonia unicialis (L.) Weber ex F.H. Wigg. (Cladoniaceae), Evernia prunastri (L.) Ach. (Parmeliaceae), Hypogymnia physodes (L.) Nyl. (Parmaliaceae), Parmelia sulcata (Taylor) (Parmeliaceae), Physcia adscendens (Fr.) H. Olivier (Physciaceae), Pseudoevernia furfuracea (L.) Zopf (Parmeliaceae), and Xanthoria parietina (L.) Th. Fr. (Teloschistaceae), were used in our experiment. We identified different metabolites in the acetone extracts of all the lichen species. Based on the high-performance liquid chromatography analysis, the content of lichen substances in the extracts was evaluated. The impact of the individual lichen-specific reference substances, compared to the lichen extracts, on the viability of keratinocytes (HaCaT cell line) and fibroblasts (BJ cell line) and on the activity of selected skin-related enzymes was investigated. Our results revealed that only emodin anthrone at a concentration of 200 mg/L was cytotoxic to keratinocytes and fibroblasts in both cell viability assays. In turn, the C. uncialis extract was only cytotoxic to keratinocytes when used at the same concentration. The other tested treatments showed a positive effect on cell viability and no cytotoxicity or indeterminate cytotoxicity (shown in only one of the tests). Elastase and collagenase activities were inhibited by most of the lichen extracts. In turn, the individual lichen compounds (with the exception of evernic acid) generally had an undesirable stimulatory effect on hyaluronidase and collagenase activity. In addition, almost all the tested compounds and extracts showed anti-inflammatory activity. This suggests that some lichen compounds hold promise as potential ingredients in dermatological and skincare products, but their safety and efficacy require further study. The high cytotoxicity of emodin anthrone highlights its potential use in the treatment of hyperproliferative skin diseases such as psoriasis.

A Comparative Study on the Effect of Vidangadi Lepa and Jeevantyadi Lepa in Eka Kushta w.s.r. to Psoriasis

Psoriasis is a chronic inflammatory and hyper proliferative skin disease. It is characterized by well-defined, erythematous scaly papules affecting about 0.1% to 3% of the population. Psoriasis can be correlated to Ekakushta which is Kapha-vata predominant. It presents with Aswedana, Mahavasthu and Matsya Shakalopama and is treated with Shodhana Karma and Bahya Chikista including Lepa Karma that occupies the prime place in its line of treatment. Acharyas have mentioned different types of Lepas and its effectiveness in skin disorders. Objective of study: To study the effect of Jeevantyadi Lepa and Vidangadi Lepa in Ekakushta and to compare its therapeutic effects in the management of Ekakushta w.s.r. to psoriasis Methods: This is a comparative clinical study with pre-test and post-test design that included 40 patients of either sex diagnosed as Ekakusta (psoriasis). All the 40 patients were randomly assigned into 2 groups with 20 patients in each. The procedure in group A involves application of Vidangadi Lepa and group B involves application of Jeevantyadi Lepa. Results: The overall results in the study revealed the statistically significant results in Group A and in Group B on all subjective and objective parameters. Conclusions: Group A and Group B had shown significant results but however Group A had an edge over to Group B.

Approach of Shoshan and Sanshaman Chikitsa in Management of Mandal Kushtha w.s.r. to Psoriasis

Psoriasis is a chronic inflammatory, hyperproliferative skin disease. It is characterised by well-defined, erythematous scaly plaques, particularly affecting extensor surfaces, scalp and nails, and usually follows a relapsing and remitting course. Psoriasis affects approximately 1.5%-3% of populations of European ancestry but is less common in Asian, South American and African populations. It occurs equally in both sexes and at any age; although it is uncommon under the age of 5 years, more than 50% of patients present before the age of 30 years. Aims and Objectives: To find out the effect of Ayurvedic medicine and Shodhan chikitsa in the management of Mandal kushtha (psoriasis). Material and Methods: A 53-year-old male patient having complaint of skin lesion on scalp, upper back and abdomen area with red demarcation from last 15 years. Lesion having silvery scales and falling all rubbing with severe itching. This condition clinically correlated to Mandal Kushtha described in Ayurveda. Mandal Kushiha has Shwelam Raklam varna, Sthirar, Styanam and Utsana Mandala (skin begins with special characters. Acharya Charaka mentioned Shodhan Chikitsa for purification of Kushtha Roga. Result and Discussion: Considering The sign and symptoms patient was treated with classical Vamana Karam (therapeutic emesis) and Virechana karma (therapeutic purgation) according in line of treatment of Kushtha (psoriasis). Assessment was done before treatment, after treatment and after follow-up. Pictures were taken before treatment and after treatment. Remarkable improvement was noticed in scaling, induration and itching after Vamana and Virechanа treatment and residue only hyper pigmented pink lesion.

Cold atmospheric plasma in combination with laser therapy provides a window for the treatment of hyperproliferative skin disease

Modern medical understanding suggests that hyperproliferative skin diseases (HSDs) are complex syndromes characterized by localized hypertrophy or hyperplasia and infiltration of inflammatory cells. Various treatments, including systemic and topical pharmacotherapy, laser interventions, photodynamic therapy, and surgery, have been proposed for managing HSDs. However, challenges such as wound healing and recurrence after laser treatment have hindered the effectiveness of laser therapy. To overcome these challenges, we conducted a study combining laser therapy with cold atmospheric plasma (CAP) for the treatment of HSDs. Seven patients with different forms of HSDs, who had not responded well to conventional treatments, were enrolled in the study. These HSDs included cases of erythroplasia of Queyrat, pyoderma gangrenosum, keloids and hypertrophic scars, cellulitis, cutaneous lichen planus, and verruca vulgaris. Laser therapy was performed to remove the hyperplastic skin lesions, followed immediately by daily CAP treatment. The results were promising, with all patients successfully treated and no recurrence observed during the follow-up periods. The combined application of CAP and laser therapy proved to be an effective and complementary strategy for managing HSDs. This innovative approach provide evidence for addressing the limitation of laser therapy by utilizing CAP to promote wound healing and mitigate inflammatory responses.Chinese Clinical Trial Registry (ChiCTR2300069993).

O22 Unravelling the pathophysiology of KLICK syndrome to identify therapeutically targetable pathways

Abstract Introduction and aims Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome is an ultrarare genodermatosis associated with a homozygous pathogenic variant, c.-95delC in POMP, which encodes for proteasome maturation protein. Clinical manifestations include linear hyperkeratotic papules in the flexures, palmoplantar keratoderma and pseudoainhum. The pathophysiology of KLICK syndrome is poorly understood, resulting in nonspecific, limited treatment options. The aim of this work is to characterize KLICK syndrome at the cellular and molecular level, with the utilization of transcriptomic techniques for potential drug repurposing. Methods A lesional skin biopsy was obtained, following informed consent, from a 32-year-old female patient with KLICK syndrome. Histology and immunostaining were used to characterize the disrupted skin architecture. RNA sequencing was used to identify key dysregulated pathways and the L1000FWD reverse transcriptomics tool enabled the generation of a shortlist of potential therapeutics for KLICK syndrome. CRISPR editing techniques and induced pluripotent stem cell (iPSC) reprogramming Methods were used to generate cellular based models carrying the pathogenic POMP variant in order to support evaluation of the shortlisted therapeutic options. Results KLICK syndrome skin histology featured hyperkeratosis, hypergranulosis and delayed cellular flattening. Consistent with pathological features, pathway analysis of transcriptomic data revealed keratinocyte differentiation and epidermis development as key upregulated pathways in KLICK syndrome. Interestingly, the Panther pathway analysis tool suggested dysregulation in epidermal growth factor receptor (EGFR) signalling, and reverse transcriptomics identified erlotinib, an EGFR inhibitor, as a potential therapeutic treatment for KLICK syndrome. HaCaT keratinocytes were successfully edited using CRISPR-Cas9 to carry the KLICK patient POMP variant and a KLICK patient iPSC line was generated to support in vitro KLICK syndrome modelling. Conclusions KLICK syndrome is a hyperproliferative inflammatory skin disorder associated with a pathogenic variant in POMP. Reverse transcriptomics is a useful tool for shortlisting drugs with biologically relevant mechanisms of action with potential for treatment of rare genetic diseases such as KLICK syndrome.

Plexin B2 tissue expression and related gene polymorphisms in psoriasis and their relation to NB-UVB and Acitretin therapy

Psoriasis is a chronic, immune-mediated, hyperproliferative skin disease. Etiopathogenesis of psoriasis is not well understood. Plexin B2 was found to have effects on CD100-mediated T-cell morphology and expressed in the immune system. It may play a role in the pathogenesis of psoriasis. To assess the tissue level of plexin-B2 and plexin B2 related gene polymorphism which is signal regulatory protein gamma (SIRPγ-rs71212732) in psoriatic patients before and after NB-UVB, acitretin therapy alone or in combination and to detect correlation between level of tissue plexin B2 and disease severity and improvement. This single blinded randomized controlled trial was carried on 50 psoriatic patients and 50 healthy controls. Psoriasis Area and Severity Index score (PASI) was used to evaluate the disease severity. Tissue plexin-b2 level was measured using ELISA and SIRPγ-rs71212732 (T\\C) was assessed using TaqMan™ assays and real-time PCR. A significant lower tissue plexin-B2 level was observed in control group (2.9 ± 0.6 pg/g) than cases (25.8 ± 2.8, pg/g) (p < 0.001). Also, a significantly higher tissue plexin-B2 level was observed in sever psoriasis (32.7 ± 3.8 pg/ml) in than moderate psoriasis (13.6 ± 2.1 pg/ml, p = 0.001). Tissue plexin B2 was positively correlated with diseases severity. Significantly higher (TC& TT) genotypes and mutant (C) allele among patients compared to the controls, p < 0.001 for all. Tissue plexin-b2 level was high in psoriasis vulgaris with positive correlation with disease severity and decreased after treatment. This may indicate a role of plexin-b2 in psoriasis vulgaris pathogenesis.

The impact of glucose conjugation on the activity and uptake of zinc phthalocyanine in HaCaT keratinocytes stimulated with proinflammatory cytokines

SignificanceGlucose metabolism has been proven as an essential process for proliferating keratinocytes, which highlights the importance of glucose transporter-1 (GLUT1) not only in the onset of psoriasis but also in the progression and severity of this inflammation-driven disease. Recent evidence showed that overexpressed GLUT1 transporter may be a potential target for the treatment of psoriasis and other hyperproliferative skin diseases. ApproachFor this reason, we attempted to synthesize and evaluate the photocytotoxic activity and intracellular uptake of glucose-conjugated zinc phthalocyanine (Glu-ZnPc), in order to prove its preferential accumulation in highly proliferative psoriatic keratinocytes. HaCaT cells stimulated with exogenous cytokines (TNF-α, IL-6, IL-17, IL-23, IL-36) were used as in vitro model. ResultsWe managed to synthesize Glu-ZnPc that is stable, water soluble, cytotoxic, and has a more efficient transport system than unconjugated ZnPc. ConclusionsWe believe that GLUT1 overexpression could potentially be utilized by using selective glucose- conjugated photosensitizers against psoriasis.

MicroRNA-21 and MicroRNA-125b expression in skin tissue and serum as predictive biomarkers for psoriasis.

Psoriasis is a chronic, inflammatory, and hyperproliferative skin disease. We have investigated the role of miR-21 and miR-125b in the development of psoriasis and atopic eczema and their relation with the severity of the diseases. Participants included 40 psoriasis patients, 40 healthy controls, and 40 atopic eczema patients as a positive control group. In addition, analysis of mRNA expression of miR-125b and miR-21 was carried out utilizing quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) in serum samples and skin tissue. Our results have demonstrated that miR-21 was significantly overexpressed in the psoriatic and atopic eczema skin tissue and serum samples compared to controls, whereas miR-125b was significantly down-expressed in psoriatic and atopic eczema skin tissues and serum samples. There was a statistically significant positive correlation between the psoriasis area and severity index (PASI) score and miR-21 among the studied groups in both serum and tissue samples. In contrast, there was a statistically significant negative association between the miR-125b and PASI score. On the other hand, there was no significant relation between the extent of body surface area (BSA), intensity, and subjective symptoms using visual analog scale (VAS) of atopic eczema disease and miRNA-21 and miRNA-125b in both tissue and serum. In conclusion, miR-21 gene expression was significantly increased in psoriatic and atopic eczema skin samples and serum samples, whereas miR-125b was statistically lowered in psoriatic and atopic eczema patient samples. The miR-21 and miR-125b expression level has a possible predictive value as a marker for psoriasis severity but not for atopic eczema severity.

Involvement of transcribed lncRNA uc.291 in hyperproliferative skin disorders

The uc.291 transcript controls keratinocytes differentiation by physical interaction with ACTL6A and subsequent induction of transcription of the genes belonging to the epidermal differentiation complex (EDC). Uc.291 is also implicated in the dedifferentiation phenotype seen in poorly differentiated cutaneous squamous cell carcinomas. Here, we would like to investigate the contribution of uc.291 to the unbalanced differentiation state of keratinocytes observed in hyperproliferative skin disorders, e. g., psoriasis. Psoriasis is a multifactorial inflammatory disease, caused by alteration of keratinocytes homeostasis. The imbalanced differentiation state, triggered by the infiltration of immune cells, represents one of the events responsible for this pathology. In the present work, we explore the role of uc.291 and its interactor ACTL6A in psoriasis skin, using quantitative real-time PCR (RT-qPCR), immunohistochemistry and bioinformatic analysis of publicly available datasets. Our data suggest that the expression of the uc.291 and of EDC genes loricrin and filaggrin (LOR, FLG) is reduced in lesional skin compared to nonlesional skin of psoriatic patients; conversely, the mRNA and protein level of ACTL6A are up-regulated. Furthermore, we provide evidence that the expression of uc.291, FLG and LOR is reduced, while ACTL6A mRNA is up-regulated, in an in vitro psoriasis-like model obtained by treating differentiated keratinocytes with interleukin 22 (IL-22). Furthermore, analysis of a publicly available dataset of human epidermal keratinocytes treated with IL-22 (GSE7216) confirmed our in vitro results. Taken together, our data reveal a novel role of uc.291 and its functional axis with ACTL6A in psoriasis disorder and a proof of concept that biological inhibition of this molecular axis could have a potential pharmacological effect against psoriasis and, in general, in skin diseases with a suppressed differentiation programme.

Dyslipidemia initiates keratinocytes proliferation through upregulation of lncRNA NEAT in psoriasis patients

BackgroundPsoriasis is a chronic inflammatory immune-mediated and hyper proliferative skin disorder that has underlying genetic factors. Psoriasis can result from interaction of cytokines between keratinocytes and T-lymphocytes. NEAT is a lncRNA involved in immune modulation and has been previously studied in cancers. This study aims to clarify the unprecedented role of NEAT in psoriasis pathogenesis.MethodsThe study was conducted on 50 healthy control subjects and 50 psoriasis patients. Blood samples from all participants were collected for analysis of their lipid profile. qRT-PCR was done for lncRNA NEAT, TNF-α, VEGF genes expression. The levels of ROS and caspase-3 were estimated by ELISA. ROC analysis was done to detect the diagnostic value of lncRNA NEAT gene expression.ResultsDyslipidemia is more prevalent among psoriasis patients. A significant up regulation in lncRNA NEAT, TNF-α, VEGF genes expression (p value˂0.001) in psoriasis patients in addition to significant increase in ROS and caspase-3 levels (p value˂0.001) in compare to controls. Additionally, a positive significant correlation between TNF-α, ROS, NEAT, caspase-3 and dyslipidemia. NEAT had an area under the curve (AUC) of 0.931 (95% CI 0.844–0.978, p < 0.001).ConclusionDyslipidemia is an initiating signal in psoriasis pathogenesis that creates a state of chronic inflammation and oxidative stress. This state induces keratinocytes proliferation and release of NEAT with subsequent caspase-3 activation to counteract the proliferating cells. NEAT could be considered as a good diagnostic biomarker for psoriasis.Graphical abstract

P18 KLICK syndrome is a hyperproliferative inflammatory skin disorder

P18 KLICK syndrome is a hyperproliferative inflammatory skin disorder

Efficacy of topically applied rapamycin-loaded redox-sensitive nanocarriers in a human skin/T cell co-culture model.

Rapamycin, also known as Sirolimus, is a promising anti-proliferative drug, but its therapeutic use for the topical treatment of inflammatory, hyperproliferative skin disorders is limited by insufficient penetration rates due to its high molecular weight (MW of 914.172g/mol) and high lipophilicity. We have shown that core multi-shell (CMS) nanocarriers sensitive to oxidative environment can improve drug delivery to the skin. In this study, we investigated the mTOR inhibitory activity of these oxidation-sensitive CMS (osCMS) nanocarrier formulations in an inflammatory ex vivo human skin model. In this model, features of inflamed skin were introduced by treating the ex vivo tissue with low-dose serine protease (SP) and lipopolysaccharide (LPS), while phorbol 12-myristate 13-acetate and ionomycin were used to stimulate IL-17A production in the co-cultured SeAx cells. Furthermore, we tried to elucidate the effects of rapamycin on single cell populations isolated from skin (keratinocytes, fibroblast) as well as on SeAx cells. Further, we measured possible effects of the rapamycin formulations on dendritic cell (DC) migration and activation. The inflammatory skin model enabled the assessment of biological readouts at both the tissue and T cell level. All investigated formulations successfully delivered rapamycin across the skin as revealed by reduced IL-17A levels. Nevertheless, only the osCMS formulations reached higher anti-inflammatory effects in the skin compared to the control formulations with a significant downregulation of mTOR activity. These results indicate that osCMS formulations could help to establish rapamycin, or even other drugs with similar physico-chemical properties, in topical anti-inflammatory therapy.

Ayurvedic Management of Stress Induced Psoriasis (Kitibha Kustha) -A Case Study

Psoriasis is a chronic, inflammatory, and hyperproliferative skin disorder. Psoriasis appears as tiny (1 to 2 cm in diameter) lesions over the upper trunk and proximal extremities. We will contrast Kitibha Kushta with it based on its clinical characteristics. About 2% of people with psoriasis have it their entire lives. Medical sciences have adopted numerous therapeutic approaches, however they come with a variety of negative effects. So in this instance, Kitibha kushtha's case was successfully treated with Shodhan, Shaman, and Bahirparimarjan chikitsa. In this single-case study, a 49-year-old male patient complained of numerous little red lesions on his chest, belly, and back of his thigh, which have been accompanied by acute itching for the past four years.Shodhan and Shirodhara were used in the patient's treatment. 90% of the patient's primary and related problems were resolved, and both during and after the end of therapy, the patient's quality of life improved. Shirodhara and Chikitsa are administered following Shodhana and Shaman. The patient's symptoms were satisfactorily relieved.

Comparative analysis of cyclin-dependent kinase 2 density by immunohistochemistry in lesional versus nonlesional psoriatic skin

Background Psoriasis is a noninfectious, inflammatory, and hyperproliferative skin disorder. Cyclin-dependent kinase 2 (CDK2) is a serine-threonine protein kinase that plays a role in the transition of G1/S, the initiation of DNA synthesis, and the regulation of the S phase exit in the cell cycle. CDK2 is uniformly expressed in healthy human epidermis being located mainly in the cytoplasm and nuclei of basal keratinocytes.Objective To compare the CDK2 density by immunohistochemistry in lesional versus nonlesional psoriatic skin and normal control and to correlate its expression with disease severity.Patients and methods This study was conducted on 30 patients with plaque psoriasis and 20 age-matched and sex-matched controls. Biopsies were obtained from the active plaque (lesional) and nonlesional skin of the patients and normal controls. CDK2 density was assessed by counting immunohistochemically positive nuclei in 1000 suprabasal keratinocytes at ×400 power fields.Results CDK2 was negative in normal control skin (no positive nuclear staining was seen in suprabasal keratinocytes). Meanwhile, the psoriatic group showed diffuse nuclear positivity in suprabasal cells. The density was significantly higher in lesional versus nonlesional skin. CDK2 density in lesional and nonlesional skin showed a statistically significant correlation with Psoriasis Area and Severity Index score (r=0.820 and 0.683, P<0.001 and <0.001, respectively).Conclusion CDK2 density is high in plaque psoriatic epidermis more than in nonlesional and control skin, and this was positively correlated with disease severity. It indicates that it may play a role in the development of psoriasis and may be a potential therapeutic target.

206 KLICK syndrome is a hyperproliferative inflammatory skin disorder

Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome is an ultra-rare autosomal recessive genodermatosis. Clinical manifestations include linear hyperkeratotic papules in the flexures, palmoplantar keratoderma and pseudoainhum. To date, all affected individuals carry a homozygous mutation, c.-95delC in POMP, which encodes for proteasome maturation protein. Disease pathophysiology is not well understood and there are no approved therapies. However, literature indicates that KLICK syndrome, like some other ichthyoses, may involve uncharacterised inflammatory pathways.

175 Yap and Notch signaling activities correlate with the two phases of skin epidermal stratification during development

The skin epidermis is transformed during development, through stratification and differentiation, from a simple single-layered epithelium into a complex barrier just before birth. However, how epidermal stratification and the switch in cell fate from the basal to suprabasal keratinocytes are achieved at the molecular level remain elusive. Understanding the crucial cell fate switch is important for designing therapies for hyperproliferative human skin diseases such as psoriasis or atopic dermatitis, which may recapitulate developmental programs.

173 A Model to Unravel Pathways Underpinning Palmoplantar Homeostasis and Disease

Tylosis with oesophageal cancer (TOC) is a rare syndrome associated with focal non-epidermolytic palmoplantar keratoderma (NEPPK), a high, lifetime risk of developing oesophageal squamous cell carcinoma (OSCC), and gain-of-function mutations in RHBDF2 (encoding iRhom2). To date, there is a lack of a useful and representative model to study the development of NEPPK and OSCC in vivo, which might aid our understanding of hyperproliferative skin disease and cancer predisposition. CRISPR-Cas9 was used to generate a novel mouse model of TOC that contains a heterozygous Rhbdf2I156T/+ mutation which mirrors the UK TOC family mutation, RHBDF2I186T/+.

Editorial: New tools and molecular advances in hyperproliferative skin disorders

Editorial: New tools and molecular advances in hyperproliferative skin disorders

Chromatin accessibility and transcriptome integrative analysis revealed AP-1-mediated genes potentially modulate histopathology features in psoriasis

BackgroundPsoriasis is a chronic and hyperproliferative skin disease featured by hyperkeratosis with parakeratosis, Munro micro-abscess, elongation of rete pegs, granulosa thinning, and lymphocyte infiltration. We previously profiled gene expression and chromatin accessibility of psoriatic skins by transcriptome sequencing and ATAC-seq. However, integrating both of these datasets to unravel gene expression regulation is lacking. Here, we integrated transcriptome and ATAC-seq of the same psoriatic and normal skin tissues, trying to leverage the potential role of chromatin accessibility and their function in histopathology features.ResultsBy inducing binding and expression target analysis (BETA) algorithms, we explored the target prediction of transcription factors binding in 15 psoriatic and 19 control skins. BETA identified 408 upregulated genes (rank product < 0.01) and 133 downregulated genes linked with chromatin accessibility. We noticed that cumulative fraction of genes in upregulation group was statistically higher than background, while that of genes in downregulation group was not significant. KEGG pathway analysis showed that the upregulated 408 genes were enriched in TNF, NOD, and IL-17 signaling pathways. In addition, the motif module in BETA suggested the 57 upregulated genes are targeted by transcription factor AP-1, indicating that increased chromatin accessibility facilitated the binding of AP-1 to the target regions and further induced expression of relevant genes. Among these genes, SQLE, STRN, EIF4, and MYO1B expression was increased in patients with hyperkeratosis, parakeratosis, and acanthosis thickening.ConclusionsIn summary, with the advantage of BETA, we identified a series of genes that contribute to the disease pathogenesis, especially in modulating histopathology features, providing us with new clues in treating psoriasis.

Vorinostat, a histone deacetylase inhibitor, as a potential novel treatment for psoriasis.

Psoriasis is characterized by aberrant activation of several pro-inflammatory circuits as well as abnormal hyperproliferation and dysregulated apoptosis of keratinocytes (KCs). Most currently available therapeutic options primarily target psoriasis-associated immunological defects rather than epidermal abnormalities. To investigate the efficacy of the histone deacetylase (HDAC) inhibitor, Vorinostat, in targeting hyperproliferation and impaired apoptosis in psoriatic skin. Vorinostat effect was investigated in primary KCs cell cultures using cell cycle analysis by flow cytometry, apoptosis assays (Annexin V-FICH and caspase-3/7) and antibody arrays, qRT-PCR and immunohistochemistry. Vorinostat impact on clinical manifestations of psoriasis was investigated in a chimeric mouse model. Vorinostat was found to inhibit KCs proliferation and to induce their differentiation and apoptosis. Using a chimeric mouse model, vorinostat was found to result in marked attenuation of a psoriasiform phenotype with a significant decrease in epidermal thickness and inhibition of epidermal proliferation. Our results support the notion that vorinostat, a prototypic HDAC inhibitor, may be of potential use in the treatment of psoriasis and other hyperproliferative skin disorders.