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Dermatology epigenetics

Chihiro Endo, Todd A Johnson, Ryoko Morino, Kazuyuki Nakazono, Shigeo Kamitsuji, Masanori Akita, Maiko Kawajiri, Tatsuya Yamasaki, Azusa Kami, Yuria Hoshi, Asami Tada, Kenichi Ishikawa, Maaya Hine, Miki Kobayashi, Nami Kurume, Yuichiro Tsunemi, Naoyuki Kamatani, Makoto Kawashima
Skin trait variation impacts quality-of-life, especially for females from the viewpoint of beauty. To investigate genetic variation related to these traits, we conducted a GWAS of various skin phenotypes in 11,311 Japanese women and identified associations for age-spots, freckles, double eyelids, straight/curly hair, eyebrow thickness, hairiness, and sweating. In silico annotation with RoadMap Epigenomics epigenetic state maps and colocalization analysis of GWAS and GTEx Project eQTL signals provided information about tissue specificity, candidate causal variants, and functional target genes...
June 12, 2018: Scientific Reports
Joshua S Mervis, Jean S McGee
The epigenetic regulation of gene expression is accomplished primarily through DNA methylation, histone modification, and gene silencing via the action of microRNAs. While previously very difficult to study, the field of epigenetics has been greatly facilitated by recent technological innovations. Alterations in the epigenome and epigenetic machinery are now known to be present in a variety of diseases, most notably cancers. Moreover, evidence has emerged that epigenetic dysregulation plays a causative role in disease pathogenesis...
May 22, 2018: Journal of Dermatological Treatment
Jinrong Zeng, Jianyun Lu
Ozone-therapy initially applied in medicine by an empirical approach, has now reached a new stage where most of the biological mechanisms of ozone action have been clarified, that refers to antimicrobial effects, immunoregulation, antioxidant defenses and epigenetic modification. Current ozone medical preparation in dermatology mainly classified as ozone hydrotherapy, ozonated oil externally used and ozone autohemotherapy (OAHT). Admittedly, ozone is widely used in various fields against gram-negative and gram-positive bacteria, viruses, and fungi...
March 2018: International Immunopharmacology
Kanad Ghosh, Kyle O'Neil, Brian C Capell
By regulating the accessibility of the genome, epigenetic regulators such as histone proteins and the chromatin-modifying enzymes that act upon them control gene expression. Proper regulation of this "histone code" allows for the precise control of transcriptional networks that are essential for establishing and maintaining cell fate and identity, disruption of which may drive carcinogenesis. How these dynamic epigenetic regulators contribute to both skin homeostasis and disease is only beginning to be understood...
March 2018: Journal of Dermatological Science
Nina Poliak, Anthony Rainey
We present a unique case of 3 vascular malformations-Sturge-Weber syndrome (SWS), facial infantile hemangioma (IH), and cutis marmorata telangiectatica congenita (CMTC)-with dermatologic manifestations presenting in the same patient. This case highlights the possibility of occurrence of multiple vascular malformations in the same patient; the potential role of epigenetic factors; and the importance of a multidisciplinary approach to diagnose, treat, and manage this complicated interplay of vascular abnormalities to achieve the best outcome...
October 2017: Cutis; Cutaneous Medicine for the Practitioner
Tatiana G Ruksha, Anna V Komina, Nadezhda V Palkina
MicroRNAs are essential regulators of various cellular processes such as cell growth, differentiation, apoptosis, and the immune response, acting as factors for translational repression and/or degradation of target messenger RNA. Currently, microRNAs are considered as promising biomarkers and therapeutic targets for different pathological conditions. Skin may serve as a convenient model for microRNA modulation studies due to the comparatively easy access to targets cells. Cutaneous diseases are characterized by multiple intercellular communication pathways, triggered by diverse stimuli and mediated by heterogenous regulators, including microRNAs...
August 1, 2017: European Journal of Dermatology: EJD
Apurba K Bandyopadhyay, Somnath Paul, Shanta Adak, Ashok K Giri
Early life exposure to arsenic has profound effect towards development of arsenic induced toxic outcomes. Some districts in the state of West Bengal, India are highly affected by arsenic, mainly through ground water. In children, not much of the toxic outcomes like dermatological lesions are observed but it is thought that the exposure leads to transient alteration in their biological processes that leads to various deleterious health effects later on. We evaluated the global methylation status by analyzing the LINE-1 methylation profile in children from arsenic exposed region between the age group 5-15 years along with the cytogenetic stress induced by arsenic as measured by lymphocyte micronucleus (MN) frequency...
August 2016: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Ya-Ping Chen, Xiao-Yang Hou, Chun-Sheng Yang, Xiao-Xiao Jiang, Ming Yang, Xi-Feng Xu, Shou-Xin Feng, Yan-Qun Liu, Guan Jiang
Malignant melanoma is an aggressive, highly lethal dermatological malignancy. Chemoresistance and rapid metastasis limit the curative effect of multimodal therapies like surgery or chemotherapy. The suicide enzyme O6-methylguanine-DNA methyltransferase (MGMT) removes adducts from the O6-position of guanine to repair DNA damage. High MGMT expression is associated with resistance to therapy in melanoma. However, it is unknown if MGMT is regulated by DNA methylation or histone acetylation in melanoma. We examined the effects of the DNA methylation inhibitor 5-Aza-2'-deoxycytidine and histone deacetylase inhibitor Trichostatin A alone or in combination on MGMT expression and promoter methylation and histone acetylation in A375, MV3, and M14 melanoma cells...
August 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Kamalika Saha, Gautam Adhikary, Richard L Eckert
PKCδ and p38δ are key proteins in a cascade that stimulates keratinocyte differentiation. This cascade activates transcription of involucrin (hINV) and other genes associated with differentiation. Protein arginine methyltransferase 5 (PRMT5) is an arginine methyltransferase that symmetrically dimethylates arginine residues. This protein interacts with a cofactor, MEP50, and symmetrically dimethylates arginine eight of histone 3 (H3R8me2s) and arginine three of histone 4 (H4R3me2s) to silence gene expression...
October 8, 2015: Journal of Investigative Dermatology
Elisabetta Damiani, Nahum Puebla-Osorio, Enrique Gorbea, Stephen E Ullrich
UV radiation-induced systemic immune suppression is a major risk factor for skin cancer induction. The migration of dermal mast cells from the skin to the draining lymph nodes has a prominent role in activating systemic immune suppression. UV-induced keratinocyte-derived platelet-activating factor (PAF) activates mast cell migration, in part by upregulating the expression of CXCR4 on the surface of mast cells. Others have indicated that epigenetic mechanisms regulate CXCR4 expression; therefore, we asked whether PAF activates epigenetic mechanisms in mast cells...
December 2015: Journal of Investigative Dermatology
Fernando Gallardo, Juan Sandoval, Angel Díaz-Lagares, Ricard Garcia, Teresa D'Altri, Jessica González, Victor Alegre, Octavio Servitje, Ana-Belén Crujeiras, Ólafur-Andri Stefánsson, Blanca Espinet, Maria-Inmaculada Hernández, Beatriz Bellosillo, Manel Esteller, Ramon-Maria Pujol, Anna Bigas, Lluis Espinosa
Notch is a family of transmembrane receptors that participate in the regulation of cell differentiation, proliferation, and stemness. Notch pathway activation has also been found associated with different human cancers including primary cutaneous T-cell lymphomas (CTCL). The elucidation of the mechanisms driving Notch activation in these particular diseases has remained elusive. Here we studied the possibility that DNA methylation at Notch pathway gene promoters and/or deregulation of Notch-associated microRNAs contribute to activate Notch in mycosis fungoides (MF)...
December 2015: Journal of Investigative Dermatology
Orla M Gannon, Lilia Merida de Long, Mehlika Hazar-Rethinam, Eleni Topkas, Liliana B Endo-Munoz, Gethin P Thomas, Ping Zhang, Nicholas A Saunders
Recent studies have reported that epigenetic mechanisms may regulate the initiation and progress of squamous differentiation in normal and transformed keratinocytes. In particular, the role of the repressive H3K27me3 mark in the regulation of squamous differentiation has been prominent. However, there is conflicting literature showing that squamous differentiation may be dependent upon or independent of changes in H3K27me3 status. In this study we have examined the binding of trimethylated H3K27 to the promoters of proliferation or differentiation genes in keratinocytes undergoing squamous differentiation in vitro and in vivo...
October 2015: Journal of Investigative Dermatology
Soonyean Hwang, Hye-Eun Kim, Michelle Min, Rekha Raghunathan, Izabela P Panova, Ruchi Munshi, Byungwoo Ryu
Aberrant HGF-MET (hepatocyte growth factor-met proto-oncogene) signaling activation via interactions with surrounding stromal cells in tumor microenvironment has significant roles in malignant tumor progression. However, extracellular proteolytic regulation of HGF activation, which is influenced by the tumor microenvironment, and its consequential effects on melanoma malignancy remain uncharacterized. In this study, we identified SPINT2 (serine peptidase inhibitor Kunitz type 2), a proteolytic inhibitor of hepatocyte growth factor activator (HGFA), which has a significant role in the suppression of the HGF-MET pathway and malignant melanoma progression...
September 2015: Journal of Investigative Dermatology
Xiaolian Gu, Elisabet Nylander, Philip J Coates, Robin Fahraeus, Karin Nylander
Epigenetic modifications by DNA methylation are associated with a wide range of diseases. Previous studies in psoriasis have concentrated on epigenetic changes in immune cells or in total skin biopsies that include stromal-associated changes. In order to improve our understanding of the role of DNA methylation in psoriasis, we sought to obtain a comprehensive DNA methylation signature specific for the epidermal component of psoriasis and to analyze methylation changes during therapy. Genome-wide DNA methylation profiling of epidermal cells from 12 patients undergoing narrow-band UVB phototherapy and 12 corresponding healthy controls revealed a distinct DNA methylation pattern in psoriasis compared with controls...
August 2015: Journal of Investigative Dermatology
Henry K Wong, Heather Gibson, Timothy Hake, Susan Geyer, Julie Frederickson, Guido Marcucci, Michael A Caligiuri, Pierluigi Porcu, Anjali Mishra
The Sézary Syndrome (SS) is an aggressive CD4+ leukemic variant of cutaneous T-cell lymphoma. Epigenetic modification of cancer cell genome is often linked to the expression of important cancer-related genes. Here we addressed the hypothesis that, in SS, DNA hypomethylation is involved in upregulation of PLS3, GATA6, and TWIST1, genes that are undetected in normal lymphocytes. Pyrosequencing analysis of CpG rich regions, and CpG dinucleotides within the 5' regulatory regions, confirmed hypomethylation of all three genes in SS, compared with controls...
August 2015: Journal of Investigative Dermatology
Elisa Penna, Francesca Orso, Daniela Taverna
MicroRNAs are short regulatory RNAs that are able to post-transcriptionally modulate gene expression and that have crucial roles in the control of physiological and pathological processes including cancer onset, growth, and progression. miR-214, located inside the sequence of the long noncoding Dmn3os transcript, contributes to the regulation of normal and cancer cell biology, even if it operates in a context-dependent and sometimes contradictory manner. miR-214 is deregulated in several human tumors including melanoma, breast, ovarian, gastric, and hepatocellular carcinomas...
April 2015: Journal of Investigative Dermatology
Jinhua Wang, Sharon K Huang, Diego M Marzese, Sandy C Hsu, Neal P Kawas, Kelly K Chong, Georgina V Long, Alexander M Menzies, Richard A Scolyer, Sivan Izraely, Orit Sagi-Assif, Isaac P Witz, Dave S B Hoon
BRAF mutations are frequent in cutaneous melanomas, and BRAF inhibitors (BRAFi) have shown remarkable clinical efficacy in BRAF mutant melanoma patients. However, acquired drug resistance can occur rapidly and tumor(s) often progresses thereafter. Various mechanisms of BRAFi resistance have recently been described; however, the mechanism of resistance remains controversial. In this study, we developed BRAFi-resistant melanoma cell lines and found that metastasis-related epithelial to mesenchymal transition properties of BRAFi-resistant cells were enhanced significantly...
February 2015: Journal of Investigative Dermatology
Christina Dahl, Cecilie Abildgaard, Rikke Riber-Hansen, Torben Steiniche, Johanne Lade-Keller, Per Guldberg
The receptor tyrosine kinase KIT and its ligand, stem cell factor (SCF), are essential for the proliferation and survival of normal melanocytes. In melanomas arising on mucosal, acral, and chronically sun-damaged skin, activating KIT mutations have been identified as oncogenic drivers and potent therapeutic targets. Through an initial whole-genome screen for aberrant promoter methylation in melanoma, we identified the KIT promoter as a target for hypermethylation in 43/110 melanoma cell lines, and in 3/12 primary and 11/29 metastatic cutaneous melanomas...
February 2015: Journal of Investigative Dermatology
Jianqiang Wu, Katrin A Salva, Gary S Wood
Mycosis fungoides and Sézary syndrome are two major forms of cutaneous T-cell lymphoma (CTCL) characterized by resistance to apoptosis. A central pathway for T-cell apoptosis is activation-induced cell death, which is triggered through the T-cell receptor (TCR). This results in upregulation of FAS ligand (FASL) and subsequent apoptosis through the FAS death receptor pathway. It has been known for more than a decade that TCR signaling is defective in CTCL; however, the underlying mechanism has not been apparent...
March 2015: Journal of Investigative Dermatology
Linda Gao, Karin van den Hurk, Peter T M Moerkerk, Jelle J Goeman, Samuel Beck, Nelleke A Gruis, Joost J van den Oord, Véronique J Winnepenninckx, Manon van Engeland, Remco van Doorn
Dysplastic nevi are melanocytic lesions that represent an intermediate stage between common nevus and melanoma. Histopathological distinction of dysplastic nevus from melanoma can be challenging and there is a requirement for molecular diagnostic markers. In this study, we examined promoter CpG island methylation of a selected panel of genes, identified in a genome-wide methylation screen, across a spectrum of 405 melanocytic neoplasms. Promoter methylation analysis in common nevi, dysplastic nevi, primary melanomas, and metastatic melanomas demonstrated progressive epigenetic deregulation...
December 2014: Journal of Investigative Dermatology
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