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Journal of Investigative Dermatology

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https://www.readbyqxmd.com/read/28528168/human-keratinocyte-differentiation-requires-translational-control-by-the-eif2%C3%AE-kinase-gcn2
#1
Ann E Collier, Ronald C Wek, Dan F Spandau
Appropriate and sequential differentiation of keratinocytes is essential for all functions of the human epidermis. While transcriptional regulation has proven to be important for keratinocyte differentiation, little is known about the role of translational control. A key mechanism for modulating translation is through phosphorylation of the α subunit of eIF2. A family of different eIF2α kinases function in the integrative stress response to inhibit general protein synthesis coincident with preferential translation of select mRNAs that participate in stress alleviation...
May 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28528167/cxcl1-inhibition-regulates-uvb-induced-skin-inflammation-and-tumorigenesis-in-xpa-deficient-mice
#2
Makoto Kunisada, Chieko Hosaka, Chihiro Takemori, Eiji Nakano, Chikako Nishigori
Xeroderma pigmentosum complementation group A (XP-A) is a hereditary disease characterized by early onset of skin cancers and freckles-like pigmented maculae in the sun-exposed sites. Although etiology of predisposition to UV-induced skin tumors in XP-A is well investigated as a repair deficiency in UV-induced DNA damage, the mechanism of exaggerated sunburn in patients with XP-A and whether UV-induced inflammation relates to skin tumor-prone phenotype remains to be elucidated. Using gene profiling of XP-A model mice, Xpa-deficient mice, we found that expression of CXCL1 in the skin and blood levels of in Xpa-deficient mice increased significantly after UVB exposure at an even a limited area in comparison to those of wild-type mice...
May 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28526302/an-important-role-of-vegf-c-in-promoting-lymphedema-development
#3
Epameinondas Gousopoulos, Steven T Proulx, Samia B Bachmann, Lothar C Dieterich, Jeannette Scholl, Sinem Karaman, Roberta Bianchi, Michael Detmar
Secondary lymphedema is a common post-cancer treatment complication but the pathomechanisms underlying the disease remain unclear. Using a mouse-tail lymphedema model, we found an increase in local and systemic levels of the lymphangiogenic factor VEGF-C, and identified CD68+ macrophages as a cellular source. Surprisingly, overexpression of VEGF-C in a transgenic mouse model led to aggravation of lymphedema with increased immune cell infiltration and vascular leakage in comparison to wild-type littermates. Conversely, blockage of VEGF-C by overexpression of soluble VEGFR3 reduced edema development, diminishing inflammation and blood vascular leakage...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28526301/mfg-e8-reprogramming-of-macrophages-promotes-wound-healing-by-increased-bfgf-production-and-fibroblast-functions
#4
Patrick Laplante, Frédéric Brillant-Marquis, Marie-Joëlle Brissette, Benjamin Joannette-Pilon, Romain Cayrol, Victor Kokta, Jean-François Cailhier
Macrophages are essential for tissue repair. They have a crucial role in cutaneous wound healing, participating actively in the inflammation phase of the process. Unregulated macrophage activation may, however, represent a source of excessive inflammation leading to abnormal wound healing and hypertrophic scars. Our research group has demonstrated that apoptotic endothelial and epithelial cells secrete Milk Fat Globule Epidermal Growth Factor-8 (MFG-E8), which has the ability to reprogram macrophages from a M1 (pro-inflammatory) to a M2 (anti-inflammatory pro-repair) phenotype...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28526300/embryonic-ap1-transcription-factor-deficiency-causes-a-collodion-baby-like-phenotype
#5
Christina A Young, Richard L Eckert, Gautam Adhikary, Debra Crumrine, Peter M Elias, Miroslav Blumenberg, Ellen A Rorke
AP1 transcription factors are important controllers of gene expression in the epidermis, and altered AP1 factor function can perturb keratinocyte proliferation and differentiation. However, our understanding of how AP1 signaling changes may underlie or exacerbate skin disease is limited. We have shown that inhibiting AP1 factor function in suprabasal adult epidermis leads to reduced filaggrin levels and to a phenotype that resembles the genetic disorder, ichthyosis vulgaris. We now show that inhibiting AP1 factor function during development in embryonic epidermis produces marked phenotypic changes including reduced filaggrin mRNA and protein levels, compromised barrier function, marked ultrastructural change and enhanced dehydration susceptibility that resembles the phenotype observed in the flaky tail mouse, a model for ichthyosis vulgaris...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28526299/mir-200a-regulates-cdk4-6-inhibitor-effect-by-targeting-cdk6-in-metastatic-melanoma
#6
Matias A Bustos, Shigeshi Ono, Diego M Marzese, Takashi Oyama, Yuuki Iida, Garrett Cheung, Nellie Nelson, Sandy C Hsu, Qiang Yu, Dave S B Hoon
Cyclin-dependent kinase (CDK) 4 and 6 pathway is frequently dysregulated in cutaneous melanoma. Recently, CDK4/6 inhibitors have shown promising clinical activity against several cancer types, including melanoma. Here, we demonstrate that miR-200a decreases CDK6 expression and thus reduces the response of CDK4/6 inhibitor in highly proliferative metastatic melanoma. Down-regulation of miR-200a expression in melanoma cells is associated with disease progression and a higher number of lymph node metastases. Furthermore, miR-200a expression is epigenetically modulated by both DNA methylation at the promoter region and chromatin accessibility of an upstream genomic region with enhancer activity...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28526298/regulation-of-the-glycerol-transporter-aquaporin-3-by-histone-deacetylase-3-and-p53-in-keratinocytes
#7
Vivek Choudhary, Lawrence O Olala, Karen Kagha, Zhi-Qiang Pan, Xunsheng Chen, Rong Yang, Abigail Cline, Inas Helwa, Lauren Marshall, Ismail Kaddour-Djebbar, Meghan E McGee-Lawrence, Wendy B Bollag
Aquaporin-3 (AQP3), a water and glycerol channel, plays an important role in epidermal function, with studies demonstrating its involvement in keratinocyte proliferation, differentiation and migration and epidermal wound healing and barrier repair. Increasing speculation about the use of histone deacetylase (HDAC) inhibitors to treat skin diseases led us to investigate HDAC's role in the regulation of AQP3. The broad-spectrum HDAC inhibitor, suberolyanilide hydroxamic acid (SAHA) induced AQP3 mRNA and protein expression in a dose- and time-dependent manner in normal keratinocytes...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28526297/modeling-the-structure-of-keratin-1-and-10-terminal-domains-and-their-misassembly-in-keratoderma
#8
Cedric Badowski, Adelene Y L Sim, Chandra Verma, Ildikó Szeverényi, Chidambaram Natesavelalar, Ana Terron-Kwiatkowski, John Harper, Edel A O'Toole, E Birgitte Lane
The terminal domains of suprabasal keratins of the skin epithelium are very resistant to evidence-based structural analysis because of their inherent flexibility and lack of predictable structure. We present a model for the structure and interactions of the head and tail domains of epidermal keratins K1 and K10, based on all-atom 3D simulations of keratin primary amino acid sequences, and tyrosine phosphorylation predictions, extracted from published databases. We observed that K1 and K10 end domains are likely to form a tetrameric terminal domain complex (TTDC) incorporating a reversibly extendable region potentially acting as a molecular spring...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28526296/mesenchymal-stem-cells-mscs-attenuate-cutaneous-sclerodermatous-graft-versus-host-disease-scl-gvhd-through-inhibition-of-immune-cell-infiltration-in-a-mouse-model
#9
Ji-Young Lim, Da-Bin Ryu, Sung-Eun Lee, Gyeongsin Park, Chang-Ki Min
Human chronic graft-versus-host disease (CGVHD) shares clinical characteristics with a murine sclerodermatous GVHD (Scl-GVHD) model that is characterized by skin thickening and lung fibrosis. A B10.D2 → BALB/c transplant model of Scl-GVHD was used to address the therapeutic effect of mesenchymal stem cells (MSCs) on the development of CGVHD. The clinical and pathological severity of cutaneous Scl-GVHD was significantly attenuated in MSC-treated recipients relative to Scl-GVHD controls. After MSC treatment, skin collagen production was significantly reduced with consistent downregulation of TGF-β expression...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28506627/rxrb-is-a-mhc-encoded-susceptibility-gene-associated-with-anti-topoisomerase-i-antibody-positive-systemic-sclerosis
#10
Akira Oka, Yoshihide Asano, Minoru Hasegawa, Manabu Fujimoto, Osamu Ishikawa, Masataka Kuwana, Yasushi Kawaguchi, Toshiyuki Yamamoto, Hiroki Takahashi, Daisuke Goto, Hirahito Endo, Masatoshi Jinnin, Shuhei Mano, Kazuyoshi Hosomichi, Tomotaka Mabuchi, Mahoko Takahashi Ueda, So Nakagawa, Stephan Beck, Seiamak Bahram, Kazuhiko Takehara, Shinichi Sato, Hironobu Ihn
Systemic sclerosis (SSc) is a systemic autoimmune and connective tissue disorder associated with the human leukocyte antigen (HLA) locus. However, the functional relationship between HLA gene(s) and disease development remains unknown. To elucidate major histocompatibility complex (MHC)-linked SSc genetics, we performed genotyping of MHC-borne microsatellites and HLA-DPB1 alleles using DNA obtained from 318 anti-topoisomerase I antibody-positive patients and 561 healthy controls, all of Japanese descent. Those results revealed 2 MHC haplotypes associated with SSc...
May 12, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28502802/topically-delivered-tumor-necrosis-factor-targeted-gene-regulation-for-psoriasis
#11
Katherine T Lewandowski, Rebecca Thiede, Nicholas Guido, Weston L Daniel, Richard Kang, Mara-Isel Guerrero-Zayas, Mark A Seeger, Xiao-Qi Wang, David A Giljohann, Amy S Paller
No abstract text is available yet for this article.
May 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28502801/genome-wide-association-reveals-pigmentation-genes-play-a-role-in-skin-aging
#12
Matthew H Law, Sarah E Medland, Gu Zhu, Seyhan Yazar, Ana Viñuela, Leanne Wallace, Sri Niranjan Shekar, David L Duffy, Veronique Bataille, Dan Glass, Tim D Spector, Diane Wood, Scott D Gordon, Julie M Barbour, Anjali K Henders, Alex W Hewitt, Grant W Montgomery, Richard A Sturm, David A Mackey, Adèle C Green, Nicholas G Martin, Stuart MacGregor
Loss of fine skin patterning is a sign of both aging and photoaging. Studies investigating the genetic contribution to skin patterning offer an opportunity to better understand a trait that influences both physical appearance and risk of keratinocyte skin cancer. We undertook a meta-analysis of genome-wide association studies (GWAS) of a measure of skin pattern (microtopography score) damage in 1,671 twin pairs and 1,745 singletons (N = 5,087) drawn from three independent cohorts. We identified that rs185146 near SLC45A2 is associated with a skin aging trait (p = 4...
May 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28502800/microrna-211-regulates-oxidative-phosphorylation-and-energy-metabolism-in-human-vitiligo
#13
Anupama Sahoo, Bongyong Lee, Katia Boniface, Julien Seneschal, Sanjaya K Sahoo, Tatsuya Seki, Chunyan Wang, Soumen Das, Xianlin Han, Michael Steppie, Sudipta Seal, Alain Taieb, Ranjan J Perera
Vitiligo is a common, chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has complex immune, genetic, environmental, and biochemical etiology, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. Here we characterized the human vitiligo cell line PIG3V and the normal human melanocytes, HEM-l by RNA-sequencing (RNA-seq), targeted metabolomics, and shotgun lipidomics...
May 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28499758/activating-cysltr2-and-plcb4-mutations-in-primary-leptomeningeal-melanocytic-tumors
#14
Johannes A P van de Nes, Christian Koelsche, Marco Gessi, Inga Möller, Antje Sucker, Richard A Scolyer, Michael E Buckland, Torsten Pietsch, Rajmohan Murali, Dirk Schadendorf, Klaus G Griewank
No abstract text is available yet for this article.
May 9, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28499757/hidradenitis-suppurativa-is-associated-with-familial-mediterranean-fever-a-population-based-study
#15
Emmilia Hodak, Lihi Atzmony, Lev Pavlovsky, Doron Comaneshter, Arnon D Cohen
No abstract text is available yet for this article.
May 9, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28499756/genetic-variants-in-wnt2b-and-btrc-predict-melanoma-survival
#16
Qiong Shi, Hongliang Liu, Peng Han, Chunying Li, Yanru Wang, Wenting Wu, Dakai Zhu, Christopher I Amos, Shenying Fang, Jeffrey E Lee, Jiali Han, Qingyi Wei
Cutaneous melanoma (CM) is the most lethal skin cancer. The Wnt pathway has an impact on development, invasion and metastasis of CM, thus likely affecting CM prognosis. Using data from a published genome-wide association study (GWAS) from The University of Texas M.D. Anderson Cancer Center, we assessed the associations of 19,830 common single-nucleotide polymorphisms (SNPs) in 151 Wnt pathway autosomal genes with CM-specific survival (CMSS) and then validated significant SNPs in another GWAS from Harvard University...
May 9, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28487088/incidence-mortality-and-trends-of-non-melanoma-skin-cancer-in-germany
#17
Ulrike Leiter, Ulrike Keim, Thomas Eigentler, Alexander Katalinic, Bernd Holleczek, Peter Martus, Claus Garbe
Increasing incidence rates (IR) of non-melanoma skin cancer (NMSC) in Caucasian populations have been described worldwide. Cancer registry data from the Saarland and Schleswig-Holstein Federal States were used to analyze incidence and mortality trends in Germany. Age-standardized rates are compared to crude rates to assess disease burden. Joinpoint regression models were used to estimate annual percentage changes and 95% confidence intervals, allowing us to assess temporal trends between 1970-2012. Incidence predictions until 2030 were based on age-period-cohort models and linear extrapolation techniques...
May 6, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28479318/identification-of-somatic-mutations-in-primary-cutaneous-diffuse-large-b-cell-lymphoma-leg-type-by-massive-parallel-sequencing
#18
Sylvain Mareschal, Anne Pham-Ledard, Pierre Julien Viailly, Sydney Dubois, Philippe Bertrand, Catherine Maingonnat, Maxime Fontanilles, Elodie Bohers, Philippe Ruminy, Isabelle Tournier, Philippe Courville, Bernard Lenormand, Anne Bénédicte Duval, Emilie Andrieu, Laurence Verneuil, Beatrice Vergier, Hervé Tilly, Pascal Joly, Thierry Frebourg, Marie Beylot-Barry, Jean-Philippe Merlio, Fabrice Jardin
To determine whether the mutational profile of primary cutaneous diffuse large B-cell lymphoma leg-type (PCLBCL-LT) is unique by comparison with other diffuse large B-cell lymphoma (DLBCL) subtypes, we analyzed a total cohort of 28 PCLBCL-LT cases by next generation sequencing with a Lymphopanel designed for DLBCL. We also analyzed 12 pairs of tumor and control DNA samples by whole exome sequencing which led us to perform resequencing of three selected genes not included in the Lymphopanel: TBL1XR1, KLHL6 and IKZF3...
May 4, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28457913/identifying-what-to-measure-in-acne-clinical-trials-first-steps-towards-development-of-a-core-outcome-set
#19
Alison M Layton, E Anne Eady, Diane M Thiboutot, Jerry Tan
No abstract text is available yet for this article.
April 27, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28457912/erdr1-attenuates-dermatophagoides-farina-body-extract-induced-atopic-dermatitis-in-nc-nga-mice
#20
Kyung Eun Kim, Myung Jin Jung, Younkyung Houh, Tae Sung Kim, Wang Jae Lee, Yoolhee Yang, Sa Ik Bang, Chang Han Kim, Heejong Kim, Hyun Jeong Park, Daeho Cho
No abstract text is available yet for this article.
April 27, 2017: Journal of Investigative Dermatology
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