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https://www.readbyqxmd.com/read/28902413/frequent-genes-in-rare-diseases-panel-based-next-generation-sequencing-to-disclose-causal-mutations-in-hereditary-neuropathies
#1
Maike F Dohrn, Nicola Glöckle, Lejla Mulahasanovic, Corina Heller, Julia Mohr, Christine Bauer, Erik Riesch, Andrea Becker, Florian Battke, Konstanze Hörtnagel, Thorsten Hornemann, Saranya Suriyanarayanan, Markus Blankenburg, Jörg B Schulz, Kristl G Claeys, Burkhard Gess, Istvan Katona, Andreas Ferbert, Debora Vittore, Alexander Grimm, Stefan Wolking, Ludger Schöls, Holger Lerche, G Christoph Korenke, Dirk Fischer, Bertold Schrank, Urania Kotzaeridou, Gerhard Kurlemann, Bianca Dräger, Anja Schirmacher, Peter Young, Beate Schlotter-Weigel, Saskia Biskup
Hereditary neuropathies comprise a wide variety of chronic diseases associated to more than 80 genes identified to date. We herein examined 612 index patients with either a Charcot-Marie-Tooth phenotype, hereditary sensory neuropathy, familial amyloid neuropathy, or small fiber neuropathy using a customized multigene panel based on the next generation sequencing (NGS) technique. In 121 cases (19.8%), we identified at least one putative pathogenic mutation. Out of these, 54.4% showed an autosomal dominant, 33...
September 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28880149/dual-function-of-the-pi3k-akt-mtorc1-axis-in-myelination-of-the-peripheral-nervous-system
#2
Gianluca Figlia, Camilla Norrmén, Jorge A Pereira, Daniel Gerber, Ueli Suter
Myelination is a biosynthetically demanding process in which mTORC1, the gatekeeper of anabolism, occupies a privileged regulatory position. We have shown previously that loss of mTORC1 function in Schwann cells (SCs) hampers myelination. Here, we genetically disrupted key inhibitory components upstream of mTORC1, TSC1 or PTEN, in mouse SC development, adult homeostasis, and nerve injury. Surprisingly, the resulting mTORC1 hyperactivity led to markedly delayed onset of both developmental myelination and remyelination after injury...
September 7, 2017: ELife
https://www.readbyqxmd.com/read/28877980/nad-metabolism-fuels-human-and-mouse-intestinal-inflammation
#3
Romana R Gerner, Victoria Klepsch, Sophie Macheiner, Kathrin Arnhard, Timon E Adolph, Christoph Grander, Verena Wieser, Alexandra Pfister, Patrizia Moser, Natascha Hermann-Kleiter, Gottfried Baier, Herbert Oberacher, Herbert Tilg, Alexander R Moschen
OBJECTIVE: Nicotinamide phosphoribosyltransferase (NAMPT, also referred to as pre-B cell colony-enhancing factor or visfatin) is critically required for the maintenance of cellular nicotinamide adenine dinucleotide (NAD) supply catalysing the rate-limiting step of the NAD salvage pathway. NAMPT is strongly upregulated in inflammation including IBD and counteracts an increased cellular NAD turnover mediated by NAD-depleting enzymes. These constitute an important mechanistic link between inflammatory, metabolic and transcriptional pathways and NAD metabolism...
September 6, 2017: Gut
https://www.readbyqxmd.com/read/28860938/early-growth-response-2-and-egr3-are-unique-regulators-in-immune-system
#4
REVIEW
Sina Taefehshokr, Yashar Azari Key, Mansour Khakpour, Pourya Dadebighlu, Amin Oveisi
The immune system is evolved to defend the body against pathogens and is composed of thousands of complicated and intertwined pathways, which are highly controlled by processes such as transcription and repression of cellular genes. Sometimes the immune system malfunctions and a break down in self-tolerance occurs. This lead to the inability to distinguish between self and non-self and cause attacks on host tissues, a condition also known as autoimmunity, which can result in chronic debilitating diseases. Early growth response genes are family of transcription factors comprising of four members, Egr1, Egr2, Egr3 and Egr4...
2017: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/28842216/egr2-enhances-insulin-resistance-via-jak2-stat3-socs-1-pathway-in-hepg2-cells-treated-with-palmitate
#5
Lin Lu, Xinhua Ye, Qing Yao, Aijiao Lu, Zhen Zhao, Yang Ding, Chuchen Meng, Wenlong Yu, Yunfeng Du, JinLuo Cheng
Insulin resistance is generally responsible for the pathogenesis of type 2 diabetes mellitus (T2DM). Early growth response proteins-2 (Egr2) has been reported to be able to increase the expression of the suppressors of cytokine signaling-1 (SOCS-1), and impair insulin signaling pathway through suppression of insulin receptor substrates (IRS), including IRS-1 and IRS-2. However, whether Egr2 is directly involved in the development of insulin resistance, and how its potential contributions to insulin resistance still remain unknown...
August 22, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28834756/regulation-of-peripheral-myelination-through-transcriptional-buffering-of-egr2-by-an-antisense-long-non-coding-rna
#6
Margot Martinez-Moreno, Timothy Mark O'Shea, John P Zepecki, Alexander Olaru, Jennifer K Ness, Robert Langer, Nikos Tapinos
Precise regulation of Egr2 transcription is fundamentally important to the control of peripheral myelination. Here, we describe a long non-coding RNA antisense to the promoter of Egr2 (Egr2-AS-RNA). During peripheral nerve injury, the expression of Egr2-AS-RNA is increased and correlates with decreased Egr2 transcript and protein levels. Ectopic expression of Egr2-AS-RNA in dorsal root ganglion (DRG) cultures inhibits the expression of Egr2 mRNA and induces demyelination. In vivo inhibition of Egr2-AS-RNA using oligonucleotide GapMers released from a biodegradable hydrogel following sciatic nerve injury reverts the EGR2-mediated gene expression profile and significantly delays demyelination...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28831138/embryonic-hindbrain-patterning-genes-delineate-distinct-cardio-respiratory-and-metabolic-homeostatic-populations-in-the-adult
#7
Jenny J Sun, Teng-Wei Huang, Jeffrey L Neul, Russell S Ray
Previous studies based on mouse genetic mutations suggest that proper partitioning of the hindbrain into transient, genetically-defined segments called rhombomeres is required for normal respiratory development and function in neonates. Less clear is what role these genes and the neurons they define play in adult respiratory circuit organization. Several Cre drivers are used to access and study developmental rhombomeric domains (Eng1 (Cre) , HoxA2-Cre, Egr2 (Cre) , HoxB1 (Cre) , and HoxA4-Cre) in the adult...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790436/three-tf-co-expression-modules-regulate-pressure-overload-cardiac-hypertrophy-in-male-mice
#8
Yao-Ming Chang, Li Ling, Ya-Ting Chang, Yu-Wang Chang, Wen-Hsiung Li, Arthur Chun-Chieh Shih, Chien-Chang Chen
Pathological cardiac hypertrophy, a dynamic remodeling process, is a major risk factor for heart failure. Although a number of key regulators and related genes have been identified, how the transcription factors (TFs) dynamically regulate the associated genes and control the morphological and electrophysiological changes during the hypertrophic process are still largely unknown. In this study, we obtained the time-course transcriptomes at five time points in four weeks from male murine hearts subjected to transverse aorta banding surgery...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28778081/multiple-regulatory-aspects-of-histone-methyltransferase-ezh2-in-pb-induced-neurotoxicity
#9
Wei-Zhen Xue, Xiaozhen Gu, Yulan Wu, Danyang Li, Yi Xu, Hui-Li Wang
Pb is a pervasive environmental threat to human health. Although remarkable progress has been made in its neurotoxicity, the precise molecular mechanisms underlying this widespread toxicant still remain elusive. In this study, the detailed roles of EZH2, a transcriptional repressor, in the regulation of Pb-led neurotoxicity were investigated, highlighting its sub-functionalization, compartmentalization, functional chaperones and downstream partners. Based on the findings, EZH2's protein levels were significantly reduced in response to Pb treatment; EZH2's gain-of-function trials recovered the dampened neurite outgrowth; EZH2' recruitment to ploycomb complex, as well as its interaction with cytosolic Vav1, was altered in a distinct manner, suggesting that EZH2's multiple roles were markedly redistributed in this context; EZH2's cytosolic and nuclear presence differed in their respective response towards Pb treatment; EZH2 directly occupied the promoters of EGR2, NGFR and CaMKK2, genes responsible for various nerve functions and repair mechanisms, and essentially contributed to their aberrant expression...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733346/regulation-and-action-of-early-growth-response-1-in-bovine-granulosa-cells
#10
Peng Han, Hilda Guerrero-Netro, Anthony Estienne, Binyun Cao, Christopher Price
Fibroblast growth factors (FGF) modify cell proliferation and differentiation through receptor tyrosine kinases, which stimulate the expression of transcription factors including members of the early growth response (EGR) family. In ovarian granulosa cells, most FGFs activate typical response genes, although the role of EGR proteins has not been described. In the present study, we determined the regulation of EGR mRNA by FGFs and explored the role of EGR1 in the regulation of FGF response genes. Addition of FGF1, FGF2, FGF4 or FGF8b increased EGR1 and EGR3 mRNA levels, whereas FGF18 increased only EGR1 mRNA abundance...
July 21, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28723564/the-lysine-acetyltransferase-gcn5-is-required-for-inkt-cell-development-through-egr2-acetylation
#11
Yajun Wang, Chawon Yun, Beixue Gao, Yuanming Xu, Yana Zhang, Yiming Wang, Qingfei Kong, Fang Zhao, Chyung-Ru Wang, Sharon Y R Dent, Jian Wang, Xiangping Xu, Hua-Bin Li, Deyu Fang
The development of CD1d-restricted invariant natural killer T (iNKT) cells, a population that is critical for both innate and adaptive immunity, is regulated by multiple transcription factors, but the molecular mechanisms underlying how the transcriptional activation of these factors are regulated during iNKT development remain largely unknown. We found that the histone acetyltransferase general control non-derepressible 5 (GCN5) is essential for iNKT cell development during the maturation stage. GCN5 deficiency blocked iNKT cell development in a cell-intrinsic manner...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28704293/analysis-of-neural-crest-cells-from-charcot-marie-tooth-disease-patients-demonstrates-disease-relevant-molecular-signature
#12
Fukiko Kitani-Morii, Keiko Imamura, Takayuki Kondo, Ryo Ohara, Takako Enami, Ran Shibukawa, Takuya Yamamoto, Kazuya Sekiguchi, Junya Toguchida, Toshiki Mizuno, Masanori Nakagawa, Haruhisa Inoue
Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy. The majority of CMT is demyelinating type (demyelinating CMT) caused by Schwann cell involvement. Although a large number of genes responsible for demyelinating CMT have been found, the common molecular target of the pathophysiology caused by these different genes in demyelinating CMT is still unknown. We generated induced pluripotent stem cells (iPSCs) from healthy controls and patients with demyelinating CMT caused by duplication in peripheral myelin protein 22 kDa (PMP22) or point mutations in myelin protein zero (MPZ) or early growth response 2 (EGR2)...
September 6, 2017: Neuroreport
https://www.readbyqxmd.com/read/28701958/a-single-dose-of-lsd-does-not-alter-gene-expression-of-the-serotonin-2a-receptor-gene-htr2a-or-early-growth-response-genes-egr1-3-in-healthy-subjects
#13
Patrick C Dolder, Edna Grünblatt, Felix Müller, Stefan J Borgwardt, Matthias E Liechti
Rationale: Renewed interest has been seen in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. The repeated use of LSD leads to tolerance that is believed to result from serotonin (5-HT) 5-HT2A receptor downregulation. In rats, daily LSD administration for 4 days decreased frontal cortex 5-HT2A receptor binding. Additionally, a single dose of LSD acutely increased expression of the early growth response genes EGR1 and EGR2 in rat and mouse brains through 5-HT2A receptor stimulation...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28687085/regulation-of-early-growth-response-2-expression-by-secreted-frizzled-related-protein-1
#14
Kelly J Gregory, Stephanie M Morin, Sallie S Schneider
BACKGROUND: Secreted frizzled-related protein 1 (SFRP1) expression is down-regulated in a multitude of cancers, including breast cancer. Loss of Sfrp1 also exacerbates weight gain as well as inflammation. Additionally, loss of SFRP1 enhances TGF-β signaling and the downstream MAPK pathway. TGF-β has been shown to increase the expression of Early Growth Response 2 (EGR2), a transcription factor implicated in immune function in a wide variety of cell types. The work described here was initiated to determine whether SFRP1 modulation affects TGF-β mediated EGR2 expression in mammary tissues as well as macrophage polarization...
July 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28636612/laminin-211-inhibits-protein-kinase-a-in-schwann-cells-to-modulate-neuregulin-1-type-iii-driven-myelination
#15
Monica Ghidinelli, Yannick Poitelon, Yoon Kyoung Shin, Dominique Ameroso, Courtney Williamson, Cinzia Ferri, Marta Pellegatta, Kevin Espino, Amit Mogha, Kelly Monk, Paola Podini, Carla Taveggia, Klaus-Armin Nave, Lawrence Wrabetz, Hwan Tae Park, Maria Laura Feltri
Myelin is required for proper nervous system function. Schwann cells in developing nerves depend on extrinsic signals from the axon and from the extracellular matrix to first sort and ensheathe a single axon and then myelinate it. Neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211) are the key axonal and matrix signals, respectively, but how their signaling is integrated and if each molecule controls both axonal sorting and myelination is unclear. Here, we use a series of epistasis experiments to show that Lm211 modulates neuregulin signaling to ensure the correct timing and amount of myelination...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28624207/identification-of-novel-fibrosis-modifiers-by-in%C3%A2-vivo-sirna-silencing
#16
Elisabeth H Vollmann, Lizhi Cao, Aldo Amatucci, Taylor Reynolds, Stefan Hamann, Isin Dalkilic-Liddle, Thomas O Cameron, Markus Hossbach, Kevin J Kauffman, Faryal F Mir, Daniel G Anderson, Tatiana Novobrantseva, Victor Koteliansky, Tatiana Kisseleva, David Brenner, Jeremy Duffield, Linda C Burkly
Fibrotic diseases contribute to 45% of deaths in the industrialized world, and therefore a better understanding of the pathophysiological mechanisms underlying tissue fibrosis is sorely needed. We aimed to identify novel modifiers of tissue fibrosis expressed by myofibroblasts and their progenitors in their disease microenvironment through RNA silencing in vivo. We leveraged novel biology, targeting genes upregulated during liver and kidney fibrosis in this cell lineage, and employed small interfering RNA (siRNA)-formulated lipid nanoparticles technology to silence these genes in carbon-tetrachloride-induced liver fibrosis in mice...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28611210/hb-egf-regulates-prss56-expression-during-mouse-decidualization-via-egfr-erk-egr2-signaling-pathway
#17
JIe Liu, Fei Gao, Yue-Fang Liu, Hai-Ting Dou, Jia-Qi Yan, Zong-Min Fan, Zeng-Ming Yang
Embryo implantation and decidualization are key steps for successful reproduction. Although numerous factors have been identified to be involved in embryo implantation and decidualization, the mechanisms underlying these processes are still unclear. Based on our preliminary data, Prss56, a trypsin-like serine protease, is strongly expressed at implantation site in mouse uterus. However, the expression, regulation and function of Prss56 during early pregnancy are still unknown. In mouse uterus, Prss56 is strongly expressed in the subluminal stromal cells at implantation site on day 5 of pregnancy compared to inter-implantation site...
June 13, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28601552/deletion-of-p2-promoter-of-gjb1-gene-a-cause-of-charcot-marie-tooth-disease
#18
R Kulshrestha, S Burton-Jones, T Antoniadi, M Rogers, Z Jaunmuktane, S Brandner, N Kiely, R Manuel, T Willis
X-linked Charcot-Marie-Tooth disease (CMT) is the second most common cause of CMT, and is usually caused by mutations in the gap junction protein beta 1 (GJB1) gene. This gene has nerve specific P2 promoter that work synergistically with SOX10 and EGR2 genes to initiate transcription. Mutation in this region is known to cause Schwann cell dysfunction. A single large family of X linked peripheral neuropathy was identified in our practice. Next generation sequencing for targeted panel assay identified an upstream exon-splicing deletion identified extending from nucleotide c...
May 4, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28576496/identification-of-zinc-finger-transcription-factor-egr2-as-a-novel-acetylated-protein
#19
Kota Noritsugu, Akihiro Ito, Yoichi Nakao, Minoru Yoshida
EGR2 is a zinc finger transcription factor that regulates myelination in the peripheral nervous system and T cell anergy. The transcriptional activity of EGR2 is known to be regulated by its co-activators and/or co-repressors. Although the activity of transcription factors is generally regulated not only by interactions with co-regulators but also posttranslational modifications including acetylation, little is known about posttranslational modifications of EGR2. Here we show that EGR2 is a novel acetylated protein...
May 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28572627/microrna-150-modulates-intracellular-ca-2-levels-in-na%C3%A3-ve-cd8-t-cells-by-targeting-tmem20
#20
Tae-Don Kim, Hong-Ryul Jung, Sang-Hwan Seo, Se-Chan Oh, Youngho Ban, Xiaoxia Tan, Jung Min Kim, Sang Hyun Lee, Duk-Su Koh, Haiyoung Jung, Young-Jun Park, Suk Ran Yoon, Junsang Doh, Sang-Jun Ha, Inpyo Choi, Philip D Greenberg
Regulation of intracellular Ca(2+) signaling is a major determinant of CD8(+) T cell responsiveness, but the mechanisms underlying this regulation of Ca(2+) levels, especially in naïve CD8(+) T cells, are not fully defined. Here, we showed that microRNA-150 (miR-150) controls intracellular Ca(2+) levels in naïve CD8(+) T cells required for activation by suppressing TMEM20, a negative regulator of Ca(2+) extrusion. miR-150 deficiency increased TMEM20 expression, which resulted in increased intracellular Ca(2+) levels in naïve CD8(+) T cells...
June 1, 2017: Scientific Reports
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