M Skrygan

Ruhr-Universität Bochum, Bochum, North Rhine-Westphalia, Germany

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Publications (63)186.94 Total impact

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    ABSTRACT: is missing (Short communication).
    No preview · Article · Jan 2016 · Acta Dermato-Venereologica
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    ABSTRACT: Since the discovery of microRNAs (miRNAs) there have been performed several studies showing perturbations in the expression of miRNAs and the miRNA expression machinery in cutaneous melanoma. Dicer, a pivotal cytosolic enzyme of miRNA maturation has shown to be affected by both somatic and germline mutations in a variety of cancers. Recent studies have shown that recurrent somatic mutations of Dicer frequently affect the metal-ion-binding sites D1709 and D1705 of its RNase IIIb domain, therefore called hot spot mutations. The present study investigates metal-ion-binding sites D1709 and D1705 of the Dicer RNase IIIb domain in cutaneous melanomas and melanoma metastasis by Sanger sequencing. All investigated samples showed wildtype sequence and no single mutation was detected. The miRNA processing enzyme Dicer of melanoma and melanoma metastasis does not appear to be affected by mutation in the metal-ion-binding sites D1709 and D1705 of its RNase IIIb domain.
    No preview · Article · Dec 2015 · Pathology & Oncology Research
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    ABSTRACT: Altered expression profiles and mutations in epigenetic modifiers, such as ten-eleven translocation 2 (TET2) enzyme and isocitrate dehydrogenase 2 (IDH2), and/or altered levels of their substrates, including 5-methylcytosin (5mc) and 5 hydroxymethylcytosine (5hmc) have recently been reported in peripheral T cell lymphomas and many other malignancies.1-8 Since there exists a lack of data in this regard on primary cutaneous T cell lymphomas (PCTCL), we aimed to assess for the first time the 5mc, 5hmc, TET2 and IDH2 status in PCTCL of the mycosis fungoides (MF) subtype.This article is protected by copyright. All rights reserved.
    No preview · Article · Sep 2015 · British Journal of Dermatology

  • No preview · Article · Dec 2014 · Journal der Deutschen Dermatologischen Gesellschaft
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    Thilo Gambichler · Sarah Terras · Marina Skrygan

    Full-text · Article · Oct 2014 · Annals of Dermatology
  • Michael Sand · Marina Skrygan
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    ABSTRACT: The quantitative real-time polymerase chain reaction (qRT-PCR) is a valuable and well-proven technique used to investigate the expression level of multiple components of the microRNA (miRNA) maturation machinery. Here, we describe how to determine the messenger RNA expression levels of components of the miRNA machinery starting from the isolation of the RNA from a tissue biopsy to performance of the qRT-PCR.
    No preview · Article · Jan 2014 · Methods in molecular biology (Clifton, N.J.)
  • T Gambichler · S Terras · M Skrygan
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    ABSTRACT: Combined treatment using salt water baths and artificial ultraviolet (UV) radiation (balneophototherapy, BPT) is a common therapeutic option for conditions such as psoriasis. However, it remains unknown whether pre-treatment with salt water soaks alter inflammatory and/or carcinogenic effects of UVB phototherapy. We aimed to investigate the impact of BPT on COX-2 gene expression and apoptosis in normal and psoriatic keratinocytes. Normal epidermis models (NEM) and psoriatic epidermis models (PEM) were treated using different salt water soaks (3% NaCl, 30% NaCl, 30% Dead Sea salt; DSS) and subsequent narrowband ultraviolet B (NB-UVB) for three consecutive days. RT-PCR was performed for cyclooxygenase 2 (COX-2), survivin, and caspase-3. Compared with untreated controls COX-2 mRNA was significantly increased in NB-UVB irradiated NEM and PEM. NB-UVB-exposed and non-exposed 30% NaCl and 30% DSS-treated NEM and PEM (except for NB-UVB-exposed and non-irradiated 30% DSS) showed significantly higher COX-2 mRNA when compared with controls and 3% NaCl. In NB-UVB-exposed 30% NaCl and 30% DSS-treated NEM and PEM survivin mRNA was significantly decreased when compared with controls and 3% NaCl. Compared with NB-UVB-exposed controls mRNA of caspase-3 was significantly increased in NB-UVB-exposed 30% NaCl and 30% DSS-treated PEM. Although BPT using high-concentrated salt water solutions is associated with increased epidermal COX-2 mRNA expression, apoptosis of keratinocytes is enhanced possibly due to the down-regulation of survivin mRNA expression. If confirmed in larger studies these observations have important implications for BPT efficacy as well as safety, particularly with regard to the risk of early carcinogenesis.
    No preview · Article · Dec 2013 · Journal of the European Academy of Dermatology and Venereology
  • T Gambichler · M Skrygan
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    ABSTRACT: The molecular mechanisms of action of salt water soaks combined with ultraviolet (UV) irradiation - balneophototherapy (BPT) - are unknown. We aimed to investigate the effect of BPT on the expression of human β-defensin-2 (hBD2) using a psoriatic epidermis model (PEM). Using real-time RT-PCR and ELISA, we studied the expression patterns of hBD2 in PEM which were treated over three consecutive days with differently concentrated salt water solutions [(3% NaCl; 30% NaCl, 30% Dead Sea salt (DSS)] and consecutive narrowband UVB exposure. mRNA of hBD2 was significantly reduced in irradiated 3% NaCl, 30% NaCl and 30% DSS soaked PEM when compared with non-irradiated PEM. ELISA for hBD2 revealed significantly reduced protein expression in irradiated 3% NaCl, 30% NaCl and 30% DSS soaked PEM when compared with non-irradiated PEM. Compared with irradiated controls and 3% NaCl soaked and irradiated PEM, BPT using 30% NaCl and 30% DSS revealed significantly decreased hBD2 protein levels. Both mono-treatment with salt water soaks and BPT of PEM result in altered expression of hBD2, whereas the effects observed are most prominent after BPT. hBD2 gene and protein expression is predominantly down-regulated following BPT indicating that this combined phototherapeutic regimen is superior to mono-UVB or salt water soaks alone with respect to normalization of hBD2 expression in psoriatic epidermis.
    No preview · Article · Nov 2013 · Journal of the European Academy of Dermatology and Venereology
  • K. Mamali · M. Skrygan · T. Gambichler

    No preview · Article · Nov 2013 · Journal der Deutschen Dermatologischen Gesellschaft
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    T Gambichler · S Terras · A Kreuter · M Skrygan
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    ABSTRACT: Epigenetics refers to functionally relevant changes in the genome other than those of DNA sequence that can lead to changes in gene expression or cellular phenotype. There is evidence that epigenetics is relevant in the pathogenesis of autoimmune diseases such as vulvar lichen sclerosus (VLS) as well as cancer, including cutaneous squamous cell carcinoma frequently associated with VLS. We aimed to study the global methylation and hydroxymethylation status in healthy controls and VLS lesions before and after long-term UVA1 treatment. We studied 12 controls and 10 patients with VLS who were treated with medium-dose UVA1 4-times weekly for 3 months. Immunohistochemistry and mutation analyses (PCR) were performed for 5-methylcytosin (5mc), 5-hydroxymethylcytosin (5hmc), isocitrate dehydrogenases (IDH), and ten-eleven translocation 2 (TET2) enzyme, respectively. After 3-month treatment, 5mc was significantly increased in VLS when compared to baseline and controls. When compared to controls, however, 5hmc levels were significantly reduced in baseline-VLS but normalised after UVA1. Compared to controls, IDH1 expression was significantly higher in treated as well as baseline-VLS. By contrast, IDH2 levels were significantly reduced in baseline-VLS as compared to controls and UVA1-treated VLS. However, gene sequencing of IDH1, IDH2, and TET2 genes did not reveal evidence for mutations. VLS is associated with altered expression of IDH enzymes and aberrant hydroxymethylation indicating an epigenetic background for the pathogenesis of VLS. UVA1 phototherapy may cause normalisation of 5hmc patterns but also global DNA hypermethylation in VLS lesions raising concerns with respect to an increased risk of photocarcinogenesis. This article is protected by copyright. All rights reserved.
    Full-text · Article · Oct 2013 · British Journal of Dermatology
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    ABSTRACT: Polymorphic light eruption (PLE) is considered an autoimmune-mediated skin condition in which the normally ultraviolet induced local immunosuppression appears to be absent leading to recognition of photo-induced auto-antigens and consecutive inflammation. We aimed to investigate T regulatory cells (Tregs) and related immunoregulatory factors in PLE lesions and controls. Skin biopsies were performed in 13 patients with UVA1-challenged PLE, 12 female patients with chronic discoid lupus erythematosus (CDLE), and 11 healthy controls who had UVA1 exposures (UVA1-controls). Immunohistochemistry and four-colour immunofluorescence studies were performed. CDLE patients and UVA1-controls showed significantly (P = 0.0001) decreased epidermal immunoreactivity for CD1a when compared to PLE. Four-colour immunofluorescence revealed a median CD4+CD25+FOXP3+ Tregs percentage of 7.6% (3.7 - 13.6%) in PLE, a median percentage of 11.7% (9.5 - 13.9%) in CDLE, and a median percentage of 3.4% (0 - 6.8%) in UVA1-controls. Compared to UVA1-controls, PLE and CDLE lesions showed significantly decreased transforming growth factor-ß1 (TGFß1) immunoreactivity in the epidermis (P = 0.0003). In PLE lesions, we observed significantly decreased interleukin 10 (IL10) expression when compared to CDLE (P = 0.022). In the dermis, nuclear factor-κB ligand (RANKL) expression was increased in UVA1-controls as compared to PLE and CDLE (P = 0.018). Similar to CDLE, UVA1-challenged PLE lesions display an altered immunoregulatory network as indicated by decreased epidermal or dermal expression of TGFß1, IL10, and RANKL and a relatively low number of Tregs particularly when compared to other inflammatory skin conditions reported in the literature. This article is protected by copyright. All rights reserved.
    No preview · Article · Sep 2013 · British Journal of Dermatology
  • T Gambichler · S Terras · M Skrygan
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    ABSTRACT: The role of transforming growth factor-β1 (TGFβ1) and Smad signalling has not been established in psoriasis treatment. We aimed to investigate the effect of combined treatment with salt water soaks and ultraviolet radiation on the expression of TGFβ1/Smad signalling proteins in a psoriatic model. We studied mRNA expression (real-time RT-PCR) of TGFβ1, TGFβ receptor type I (TGFβRI), Smad2, Smad3, Smad4, Smad7, minichromosome maintenance protein 7, and involucrin in normal as well as psoriatic epidermis models (PEM) which were treated for three consecutive days with differently concentrated salt water solutions [(3% NaCl; 30% NaCl, 30% Dead Sea salt water (DSSW)] and subsequent narrowband ultraviolet B (NB-UVB). In PEM, TGFβ1 and Smad3 was significantly increased as compared to normal epidermis models. By contrast, TGFβRI mRNA was significantly decreased in PEM. Significant increase of mRNA levels of TGFβ1, TGFβRI, Smad2 and Smad3 was predominantly observed in non-irradiated and irradiated PEM pre-treated with 30% NaCl and/or DSSW which was paralleled by increase of involucrin mRNA. In PEM pre-treated with DSSW, TGFβRI, Smad2, Smad3, Smad4, and Smad7 mRNA was significantly higher in irradiated PEM when compared to non-irradiated samples. It has been shown that TGFβ1/Smad signalling is altered in a psoriatic model and may play a role in the mode of action of salt water soaks and NB-UVB phototherapy of psoriasis.
    No preview · Article · Jul 2013 · Cytokine
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    ABSTRACT: Background Glutathione S-transferases (GSTs) are involved in detoxification of xenobiotics such as fumaric acid esters (FAE). Objectives To perform GSTT1 geno- and phenotyping in psoriasis patients treated with FAE to find out whether the responder status and/or occurrence of side-effects are associated with allelic variants and enzymatic activity of GSTT1. Methods We treated 106 psoriasis patients with FAE. GSTT1 genotyping was performed using PCR, phenotyping was carried out by means of a validated high performance liquid chromatography assay at baseline and under treatment. ResultsThe distribution of GSTT1 genotypes was as follows: 31% *A/*A; 49% *A/*0; 20% *0/*0. GSTT1 phenotypes as expressed in enzyme activity significantly differed between conjugators classes. (P<0.001). GSTT1 activity under treatment was significantly (P=0.0001) increased when compared with baseline. There were no significant associations between the aforementioned GSTT1 pheno- and genotypes and clinical parameters such as psoriasis area and severity index (PASI)50, adverse effects and FAE dosage (P>0.05), except for the frequent occurrence of reduction (>50%) of circulating lymphocytes in patients with *0/*0 GSTT1 status (P=0.036; odds ratio: 6, 95% CI: 1.1-32). ConclusionGSTT1 geno- and phenotypes significantly correlate in psoriasis patients and do not substantially differ from healthy controls. Response to FAE does likely not depend on GSTT1. However, *0/*0 GSTT1 status is a predictor for the occurrence of marked reduction of lymphocyte counts under FAE therapy. Notably, FAE seem to enhance GSTT1 enzyme activity in high and low conjugators.
    No preview · Article · Mar 2013 · Journal of the European Academy of Dermatology and Venereology
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    Thilo Gambichler · Michael Sand · Marina Skrygan
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    ABSTRACT: Several research groups have recently reported on markedly reduced levels of 5-hydroxymethylcytosine (5hmC) in human breast, liver, lung, pancreatic, colon, prostate, brain, and myeloid cancers. We studied benign compound nevi (BCN, n=17), dysplastic compound nevi (DCN, n=15), superficial spreading melanomas [SSM, stratified in <1 mm (n=19) and >4 mm (n=18) Breslow tumor thickness], and cutaneous metastatic disease (CMD, n=24). Immunohistochemistry included specific antibodies against 5hmC, 5-methylcytosine (5mC), and ten-eleven translocation 2 protein (TET2). Immunohistological scoring showed significantly (P<0.0001) higher median 5hmC levels in BCN and DCN than in thin SSM, thick SSM, and CMD. 5mC immunoreactivity did not differ significantly (P=0.15) between nevi and melanoma. The intensity of TET2 expression was predominantly weak but was found to be significantly (P<0.0001) more often in nevi than in thin SSM, thick SSM, and CMD. We have shown that 5hmC levels and TET2 expression are significantly reduced in advanced melanomas compared with nevi and thin melanomas. It is suggested that 5hmC and TET2 possibly play an important role in the epigenetic regulation of melanoma development and progression.
    Full-text · Article · Mar 2013 · Melanoma research
  • T Gambichler · M Skrygan
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    ABSTRACT: Mid-dermal elastolysis (MDE) is a rare disorder that is histopathologically characterized by selective loss of elastic fibres in the mid-dermis. Aetiopathogenesis of MDE is still obscure. We report for the first time on the expression of lysyl oxidase-like (LOXL) proteins in lesional and non-lesional skin of a patient with reticular variant of MDE. Real-time RT-PCR and immunohistochemistry were performed for matrix metalloproteinase-2 (MMP2), MMP7, MMP9, LOXL1, LOXL2, and LOXL3. LOXL1 and LOXL3 mRNA levels in lesional skin did not substantially differ from mRNA levels measured in healthy skin. For LOXL2, however, we found decreased mRNA expression in lesional skin as compared to healthy skin. mRNA expression of MMP2 and MMP7 of lesional skin did not substantially differ from healthy skin. However, MMP9 mRNA expression was massively increased in lesional skin when compared to healthy skin. Immunohistochemistry confirmed the altered expression of LOXL2 and MMP9 in lesional skin. In conclusion, our preliminary data suggest that not only increased elastolytic activity (e.g. MMP9 up-regulation) but also affected elastin renewal due to reduced LOXL expression may contribute to the pathogenesis of MDE. More research is warranted in MDE especially with regard to the LOX family, fibulins, fibrillins, and desmosines.
    No preview · Article · Dec 2012 · Archives for Dermatological Research
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    ABSTRACT: The microprocessor complex mediates intranuclear biogenesis of precursor microRNAs from the primary microRNA transcript. Extranuclear, mature microRNAs are incorporated into the RNA-induced silencing complex (RISC) before interaction with complementary target mRNA leads to transcriptional repression or cleavage. In this study, we investigated the expression profiles of the microprocessor complex subunit DiGeorge syndrome critical region gene 8 (DGCR8) and the RISC components argonaute-1 (AGO1), argonaute-2 (AGO2), as well as double-stranded RNA-binding proteins PACT, TARBP1, and TARBP2 in epithelial skin cancer and its premalignant stage. Patients with premalignant actinic keratoses (AK, n = 6), basal cell carcinomas (BCC, n = 15), and squamous cell carcinomas (SCC, n = 7) were included in the study. Punch biopsies were harvested from the center of the tumors (lesional), from healthy skin sites (intraindividual controls), and from healthy skin sites in a healthy control group (n = 16; interindividual control). The DGCR8, AGO1, AGO2, PACT, TARBP1, and TARBP2 mRNA expression levels were detected by quantitative real-time reverse transcriptase polymerase chain reaction. The DGCR8, AGO1, AGO2, PACT, and TARBP1 expression levels were significantly higher in the AK, BCC, and SCC groups than the healthy controls (P < 0.05). There was no significant difference in the TARBP2 expression levels between groups (P > 0.05). This study indicates that major components of the miRNA pathway, such as the microprocessor complex and RISC, are dysregulated in epithelial skin cancer. © 2011 Wiley Periodicals, Inc.
    No preview · Article · Nov 2012 · Molecular Carcinogenesis
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    ABSTRACT: Acne inversa is a chronic, suppurative relapsing inflammatory skin disease that primarily affects the axillae, perineum and inframammary regions. Evidence suggests that the innate immune system is involved in the pathogenesis of acne inversa. To investigate the role of the innate immune system in acne inversa. Skin biopsies were obtained from inflammatory skin lesions (n=17) and from non-lesional skin (intraindividual control, n=17) of patients with acne inversa. Additional skin lesions were taken from patients with chronic venous leg ulcers (interindividual control, n=5). Quantitative real-time reverse transcription-polymerase chain reaction was used to determine the mRNA levels of antimicrobial peptides and proteins (AMPs), including human β-defensin (hBD)-1, hBD-2 and hBD-3, LL-37 (cathelicidin) and Ribonuclease 7 (RNase 7). mRNA levels were also determined for inflammatory and anti-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-1 (MMP1), interleukin (IL)-1β, IL-6, IL-8 and IL-10. The mRNA levels of hBD-2, LL-37, IL-1β, IL-6, IL-8, IL-10 and MMP1 were significantly higher in acne inversa lesions compared to non-lesional skin (p<0.05). A significant positive correlation expression was observed between hBD-2 mRNA expression and LL-37 (ρ=0.53, p=0.03), and between hBD-2 and RNAse 7 (ρ=0.68, p=0.006). When compared to the chronic venous leg ulcer lesions, acne inversa lesions showed a significantly higher expression of RNase 7 mRNA, while IL-1 β, IL-6, IL-8, TNF-α and MMP1 mRNA expression was significantly higher in the chronic venous leg ulcer lesions (p<0.05). The AMP, cytokine milieu and tissue proteases in acne inversa lesions differ significantly from non-lesional skin and chronic venous leg ulcers. The positively correlating up-regulation of AMPs in acne inversa indicates an important role of the innate immune system in the pathogenesis of this disorder.
    Full-text · Article · Nov 2012 · Annals of Dermatology
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    ABSTRACT: Perturbations in microRNA (miRNA) expression profiles have been reported for cutaneous malignant melanoma (CMM) predominantly when examined in cell lines. Despite the rapidly growing number of newly discovered human miRNA sequences, the availability of up-to-date miRNA expression profiles for clinical samples of primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM), and benign melanocytic nevi (BMN) is limited. Specimens excised from the center of tumors (lesional) from patients with PCMM (n=9), CMMM (n=4), or BMN (n=8) were obtained during surgery. An exploratory microarray analysis was performed by miRNA expression profiling based on Agilent platform screening for 1205 human miRNAs. The results from the microarray analysis were validated by TaqMan quantitative real-time polymerase chain reaction. In addition to several miRNAs previously known to be associated with CMM, 19 unidentified miRNA candidates were found to be dysregulated in CMM patient samples. Among the 19 novel miRNA candidates, the genes hsa-miR-22, hsa-miR-130b, hsa-miR-146b-5p, hsa-miR-223, hsa-miR-301a, hsa-miR-484, hsa-miR-663, hsa-miR-720, hsa-miR-1260, hsa-miR-1274a, hsa-miR-1274b, hsa-miR-3663-3p, hsa-miR-4281, and hsa-miR-4286 were upregulated, and the genes hsa-miR-24-1*, hsa-miR-26a, hsa-miR-4291, hsa-miR-4317, and hsa-miR-4324 were downregulated. The results of this study partially confirm previous CMM miRNA profiling studies identifying miRNAs that are dysregulated in CMM. However, we report several novel miRNA candidates in CMM tumors; these miRNA sequences require further validation and functional analysis to evaluate whether they play a role in the pathogenesis of CMM.
    No preview · Article · Oct 2012 · Cell and Tissue Research
  • N. Scola · M. Skrygan · U. Wieland · A. Kreuter · T. Gambichler
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    ABSTRACT: Congenital unilateral linear porokeratosis (CULP) is a rare disorder of keratinization that shares clinical and molecular similarities with psoriasis. It also has an increased risk for malignant transformation to cutaneous squamous cell carcinoma (SCC). We investigated the expression of psoriasin, human beta‐defensin‐2, cathelicidin antimicrobial peptide/LL‐37, e‐cadherin, involucrin, p16INK4a, p53, cyclin D1 and microchromosome maintenance protein 7 in healthy skin and in lesions of psoriasis, CULP and SCC from the same patient. p16INK4a was overexpressed in CULP but not in the subsequent SCC. Psoriasin was overexpressed in psoriasis, CULP and SCC compared with healthy skin. Speculatively, p16INK4a and psoriasin could be involved in the pathogenesis of CULP. Moreover, psoriasin may play a role in the malignant transformation of CULP to SCC.
    No preview · Article · Oct 2012 · Clinical and Experimental Dermatology
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    ABSTRACT: BACKGROUND: MicroRNAs (miRNAs) are a novel class of short RNAs that are capable epigenetically regulating gene expression in eukaryotes. MicroRNAs have been shown to be dysregulated in a variety of cancers. The data on miRNA expression in cutaneous squamous cell carcinoma (cSCC) are very limited, and microarray-based miRNA expression profiles of cSCC have not yet been determined. OBJECTIVE: To describe differentially expressed miRNAs in cSCC. METHODS: Seven patients with cSCC were enrolled in the present study. Tumor biopsies (n=7) were taken from the center of each tumor. Adjacent healthy skin (n=7) was biopsied as a control (intraindividual control). miRNA expression profiles of all specimens were detected by microarray miRNA expression profiling based on miRBAse 16 scanning for 1205 potential human miRNA target sequences. The microarray results were confirmed by TaqMan quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Non-stringent filtering with a non-adjusted p≤0.05 revealed thirteen up-regulated and eighteen down-regulated miRNAs. Non-stringent filtering with a non-adjusted p≤0.01 revealed three up-regulated (hsa-miR-135b, hsa-miR-424 and hsa-miR-766) and six down-regulated (hsa-miR-30a*, hsa-miR-378, hsa-miR-145, hsa-miR-140-3p, hsa-miR-30a and hsa-miR-26a) miRNAs in cSCC. CONCLUSION: This study reveals differentially expressed miRNAs that may play a role in the molecular pathogenesis of cSCC and that are excellent candidates for further validation and functional analysis.
    No preview · Article · Sep 2012 · Journal of dermatological science

Publication Stats

1k Citations
186.94 Total Impact Points


  • 2005-2014
    • Ruhr-Universität Bochum
      • Department of Plastic Surgery
      Bochum, North Rhine-Westphalia, Germany
  • 2006
    • St. Josef-Hospital
      Bonn, North Rhine-Westphalia, Germany