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https://www.readbyqxmd.com/read/29148104/neuregulin-1-promotes-remyelination-and-fosters-a-pro-regenerative-inflammatory-response-in-focal-demyelinating-lesions-of-the-spinal-cord
#1
Hardeep Kataria, Arsalan Alizadeh, Ghazaleh M Shahriary, Shekoofeh Saboktakin Rizi, Ryan Henrie, Kallivalappil T Santhosh, James A Thliveris, Soheila Karimi-Abdolrezaee
Oligodendroglial cell death and demyelination are hallmarks of neurotrauma and multiple sclerosis that cause axonal damage and functional impairments. Remyelination remains a challenge as the ability of endogenous precursor cells for oligodendrocyte replacement is hindered in the unfavorable milieu of demyelinating conditions. Here, in a rat model of lysolecithin lysophosphatidyl-choline (LPC)-induced focal demyelination, we report that Neuregulin-1 (Nrg-1), an important factor for oligodendrocytes and myelination, is dysregulated in demyelinating lesions and its bio-availability can promote oligodendrogenesis and remyelination...
November 17, 2017: Glia
https://www.readbyqxmd.com/read/29141020/genomic-analysis-of-atypical-fibroxanthoma
#2
Kevin Lai, Catherine A Harwood, Karin J Purdie, Charlotte M Proby, Irene M Leigh, Namita Ravi, Thaddeus W Mully, Lionel Brooks, Priscilla M Sandoval, Michael D Rosenblum, Sarah T Arron
Atypical fibroxanthoma (AFX), is a rare type of skin cancer affecting older individuals with sun damaged skin. Since there is limited genomic information about AFX, our study seeks to improve the understanding of AFX through whole-exome and RNA sequencing of 8 matched tumor-normal samples. AFX is a highly mutated malignancy with recurrent mutations in a number of genes, including COL11A1, ERBB4, CSMD3, and FAT1. The majority of mutations identified were UV signature (C>T in dipyrimidines). We observed deletion of chromosomal segments on chr9p and chr13q, including tumor suppressor genes such as KANK1 and CDKN2A, but no gene fusions were found...
2017: PloS One
https://www.readbyqxmd.com/read/29133385/targeted-next-generation-sequencing-of-cancer-genes-in-poorly-differentiated-thyroid-cancer
#3
Tiemo S Gerber, Arno Schad, Nils Hartmann, Erik Springer, Ulrich Zechner, Thomas J Musholt
Poorly differentiated thyroid carcinoma (PDTC) is a rare malignancy with higher mortality than well-differentiated thyroid carcinoma. The histological diagnosis can be difficult as well as the therapy. Improved diagnosis and new targeted therapies require knowledge of DNA sequence changes in cancer-relevant genes. The TruSeq Amplicon Cancer Panel was used to screen cancer genomes from 25 PDTC patients for somatic single nucleotide variants in 48 genes known to represent mutational hotspots. A total of 4490 variants were found in 23 tissue samples of PDTC...
November 13, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29125883/a-genetic-variant-of-mir-335-binding-site-in-the-erbb4-3-utr-is-associated-with-prognosis-of-ovary-cancer
#4
Ping Wei, Ling Li, Zhihu Zhang, Wei Zhang, Ming Liu, Xiugui Sheng
BACKGROUND: Ovarian cancer is one of the leading gynecologic malignancies globally, the 5-year survival rate for patients with advanced stage ovarian cancer is very low. Our objective was to test the hypothesis that miR-335 was associated with the survival of patients with ovarian cancer. METHOD: Bioinformatics tools and luciferase report assay were used to select the target of miR-335, and real-time PCR was used to detect the expression of miR-335 and ERBB4 in different genotype groups...
November 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29114105/neuregulin-3-signaling-mediates-nicotine-dependent-synaptic-plasticity-in-the-orbitofrontal-cortex-and-cognition
#5
Luyi Zhou, Miranda L Fisher, Robert D Cole, Thomas J Gould, Vinay Parikh, Pavel I Ortinski, Jill R Turner
Neuregulin 3 (NRG3) and ErbB4 have been linked to nicotine addiction; however, the neuronal mechanisms and behavioral consequences of NRG3-ErbB4 sensitivity to nicotine remain elusive. Recent literature suggests that relapse to smoking is due to a lack of impulsive control, which is thought to be due to altered functioning within the orbitofrontal cortex (OFC). Therefore, we examined circuitry changes within this structure following nicotine application. We report that nicotine controls synaptic plasticity in the OFC through NRG3/ErbB4-dependent regulation of GABAergic inhibition...
November 7, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29102563/tgf-%C3%AE-mediates-renal-fibrosis-via-the-smad3-erbb4-ir-long-noncoding-rna-axis
#6
Min Feng, Patrick Ming-Kuen Tang, Xiao-Ru Huang, Si-Fan Sun, Yong-Ke You, Jun Xiao, Lin-Li Lv, An-Ping Xu, Hui-Yao Lan
Transforming growth factor β (TGF-β)/Smad3 signaling plays a role in tissue fibrosis. We report here that Erbb4-IR is a novel long non-coding RNA (lncRNA) responsible for TGF-β/Smad3-mediated renal fibrosis and is a specific therapeutic target for chronic kidney disease. Erbb4-IR was induced by TGF-β1 via a Smad3-dependent mechanism and was highly upregulated in the fibrotic kidney of mouse unilateral ureteral obstructive nephropathy (UUO). Silencing Erbb4-IR blocked TGF-β1-induced collagen I and alpha-smooth muscle actin (α-SMA) expressions in vitro and effectively attenuated renal fibrosis in the UUO kidney by blocking TGF-β/Smad3 signaling...
October 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29079173/general-paucity-of-genomic-alteration-and-low-tumor-mutation-burden-in-refractory-and-metastatic-hepatoblastoma-comprehensive-genomic-profiling-study
#7
Hwajeong Lee, Tony El Jabbour, Sanaz Ainechi, Laurie M Gay, Julia A Elvin, Jo-Anne Vergilio, James Suh, Shakti H Ramkissoon, Siraj M Ali, Alexa Schrock, David Fabrizio, Garrett Frampton, Tipu Nazeer, Vincent A Miller, Philip J Stephens, Jeffrey S Ross
Hepatoblastoma (HBL) is hepatic malignancy of infants and young children which is often cured by combinations of surgery and chemotherapy. Management of refractory and metastatic HBL is challenging. Comprehensive genomic profiling was performed on 31 refractory and metastatic HBL using a hybrid-capture, adaptor ligation based next generation sequencing assay. Tumor mutation burden (TMB) was calculated from a minimum of 1.11Mb of sequenced DNA and reported as mutations/Mb. The results were analyzed for all classes of genomic alterations (GA)...
October 24, 2017: Human Pathology
https://www.readbyqxmd.com/read/28993723/bace1-dependent-neuregulin-1-signaling-an-implication-for-schizophrenia
#8
REVIEW
Zhengrong Zhang, Jing Huang, Yong Shen, Rena Li
Schizophrenia is a chronic psychiatric disorder with a lifetime prevalence of about 1% in the general population. Recent studies have shown that Neuregulin-1 (Nrg1) is a candidate gene for schizophrenia. At least 15 alternative splicing of NRG1 isoforms all contain an extracellular epidermal growth factor (EGF)-like domain, which is sufficient for Nrg1 biological activity including the formation of myelin sheaths and the regulation of synaptic plasticity. It is known that Nrg1 can be cleaved by β-secretase (BACE1) and the resulting N-terminal fragment (Nrg1-ntf) binds to receptor tyrosine kinase ErbB4, which activates Nrg1/ErbB4 signaling...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28984303/analysis-of-clinically-relevant-somatic-mutations-in-high-risk-head-and-neck-cutaneous-squamous-cell-carcinoma
#9
Catherine Zilberg, Matthew Weicai Lee, Bing Yu, Bruce Ashford, Spiridoula Kraitsek, Marie Ranson, Kerwin Shannon, Mark Cowley, N Gopalakrishna Iyer, Carsten E Palme, Sydney Ch'ng, Tsu-Hui Hubert Low, Sandra O'Toole, Jonathan R Clark, Ruta Gupta
Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequencing of 48 clinically relevant genes was performed on DNA extracted from formalin-fixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non-metastatic at minimum follow-up of 24 months...
October 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28974580/sumoylation-regulates-nuclear-accumulation-and-signaling-activity-of-the-soluble-intracellular-domain-of-the-erbb4-receptor-tyrosine-kinase
#10
Anna Maria Knittle, Maria Helkkula, Mark S Johnson, Maria Sundvall, Klaus Elenius
Erb-B2 receptor tyrosine kinase 4 (ErbB4) is a kinase that can signal via a proteolytically released intracellular domain (ICD) in addition to classical receptor tyrosine kinase-activated signaling cascades. Previously, we have demonstrated that ErbB4 ICD is posttranslationally modified by the small ubiquitin-like modifier (SUMO) and functionally interacts with the PIAS3 SUMO E3 ligase. However, direct evidence of SUMO modification in ErbB4 signaling has remained elusive. Here, we report that the conserved lysine residue 714 in the ErbB4 ICD undergoes SUMO modification, which was reversed by sentrin-specific proteases (SENPs) 1, 2 and 5...
October 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28922560/betacellulin-regulates-the-proliferation-and-differentiation-of-retinal-progenitor-cells-in-vitro
#11
Dandan Zhang, Bingqiao Shen, Yi Zhang, Ni Ni, Yuyao Wang, Fan Xianqun, Hao Sun, Ping Gu
Retinal progenitor cells (RPCs) hold great potential for the treatment of retinal degenerative diseases. However, their proliferation capacity and differentiation potential towards specific retinal neurons are limited, which limit their future clinical applications. Thus, it is important to improve the RPCs' ability to proliferate and differentiate. Currently, epidermal growth factor (EGF) is commonly used to stimulate RPC growth in vitro. In this study, we find that betacellulin (BTC), a member of the EGF family, plays important roles in the proliferation and differentiation of RPCs...
September 18, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28916792/smartflares-fail-to-reflect-their-target-transcripts-levels
#12
Maria Czarnek, Joanna Bereta
SmartFlare probes have recently emerged as a promising tool for visualisation and quantification of specific RNAs in living cells. They are supposed to overcome the common drawbacks of current methods for RNA analysis: the need of cell fixation or lysis, or the requirements for genetic manipulations. In contrast to the traditional methods, SmartFlare probes are also presumed to provide information on RNA levels in single cells. Disappointingly, the results of our comprehensive study involving probes specific to five different transcripts, HMOX1, IL6, PTGS2, Nrg1, and ERBB4, deny the usefulness of SmartFlare probes for RNA analysis...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28892072/neuregulin-signaling-pathway-in-smoking-behavior
#13
R Gupta, B Qaiser, L He, T S Hiekkalinna, A B Zheutlin, S Therman, M Ollikainen, S Ripatti, M Perola, V Salomaa, L Milani, T D Cannon, P A F Madden, T Korhonen, J Kaprio, A Loukola
Understanding molecular processes that link comorbid traits such as addictions and mental disorders can provide novel therapeutic targets. Neuregulin signaling pathway (NSP) has previously been implicated in schizophrenia, a neurodevelopmental disorder with high comorbidity to smoking. Using a Finnish twin family sample, we have previously detected association between nicotine dependence and ERBB4 (a neuregulin receptor), and linkage for smoking initiation at the ERBB4 locus on 2q33. Further, Neuregulin3 has recently been shown to associate with nicotine withdrawal in a behavioral mouse model...
August 22, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28889394/evaluation-of-protein-levels-of-the-receptor-tyrosine-kinase-erbb3-in-serum
#14
Leandro S D'Abronzo, Chong-Xian Pan, Paramita M Ghosh
The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases (RTK) consists of four members: EGFR1/ErbB1/HER1, ErbB2/HER2, ErbB3/HER3, and HER4/ErbB4. Signaling through these receptors regulates many key cellular activities, such as cell division, migration, adhesion, differentiation, and apoptosis. The ErbB family has been shown to be overexpressed in different types of cancers and is a target of several inhibitors already in clinical trials. ErbB3 lacks a functional tyrosine kinase domain and therefore has not been as extensively studied as the other members of this family, but its importance in activating downstream pathways, such as the PI3K/Akt pathway, makes this RTK a worthy investigation target, especially in urothelial carcinoma where the PI3K/Akt pathway is vital for progression...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28889094/analysis-of-known-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia-genes-reveals-a-substantial-genetic-burden-in-patients-manifesting-both-diseases-not-carrying-the-c9orf72-expansion-mutation
#15
Oriol Dols-Icardo, Alberto García-Redondo, Ricardo Rojas-García, Daniel Borrego-Hernández, Ignacio Illán-Gala, José Luís Muñoz-Blanco, Alberto Rábano, Laura Cervera-Carles, Alexandra Juárez-Rufián, Nino Spataro, Noemí De Luna, Lucía Galán, Elena Cortes-Vicente, Juan Fortea, Rafael Blesa, Oriol Grau-Rivera, Alberto Lleó, Jesús Esteban-Pérez, Ellen Gelpi, Jordi Clarimón
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of a clinical, pathological and genetic continuum. OBJECTIVES: The purpose of the present study was to assess the mutation burden that is present in patients with concurrent ALS and FTD (ALS/FTD) not carrying the chromosome 9 open reading frame 72 (C9orf72) hexanucleotide repeat expansion, the most important genetic cause in both diseases. METHODS: From an initial group of 973 patients with ALS, we retrospectively selected those patients fulfilling diagnostic criteria of concomitant ALS and FTD lacking the repeat expansion mutation in C9orf72...
September 9, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28887860/regulation-of-radial-glial-process-growth-by-glutamate-via-mglur5-trpc3-and-neuregulin-erbb4
#16
Lauri M Louhivuori, Pauli M Turunen, Verna Louhivuori, Venkatram Yellapragada, Tommy Nordström, Per Uhlén, Karl E Åkerman
Radial glial cells play an essential role through their function as guides for neuronal migration during development. Disruption of metabotropic glutamate receptor 5 (mGluR5) function retards the growth of radial glial processes in vitro. Neuregulins (NRG) are activated by proteolytic cleavage and regulate (radial) glial maintenance via ErbB3/ErbB4 receptors. We show here that blocking ErbB4 disrupts radial process extension. Soluble NRG acting on ErbB4 receptors is able to promote radial process extension in particular where process elongation has been impeded by blockade of mGluR5, the nonselective cation channel canonical transient receptor potential 3 (TRPC3), or matrix metalloproteases (MMP)...
January 2018: Glia
https://www.readbyqxmd.com/read/28886748/erbb3-drives-mammary-epithelial-survival-and-differentiation-during-pregnancy-and-lactation
#17
Michelle M Williams, David B Vaught, Meghan Morrison Joly, Donna J Hicks, Violeta Sanchez, Philip Owens, Bushra Rahman, David L Elion, Justin M Balko, Rebecca S Cook
BACKGROUND: During pregnancy, as the mammary gland prepares for synthesis and delivery of milk to newborns, a luminal mammary epithelial cell (MEC) subpopulation proliferates rapidly in response to systemic hormonal cues that activate STAT5A. While the receptor tyrosine kinase ErbB4 is required for STAT5A activation in MECs during pregnancy, it is unclear how ErbB3, a heterodimeric partner of ErbB4 and activator of phosphatidyl inositol-3 kinase (PI3K) signaling, contributes to lactogenic expansion of the mammary gland...
September 8, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28881753/sirna-mediated-inactivation-of-her3-improves-the-antitumour-activity-and-sensitivity-of-gefitinib-in-gastric-cancer-cells
#18
Heng-Heng Yuan, Ying-Nan Yang, Jian-Hua Zhou, Yan-Jing Li, Li-Ying Wang, Jun-Wei Qin, Tao Liu, Zhen-Zhen Li, Qing-Xin Zhou, Xiao-Li Wei, Ting-Ting Zhang, Peng Huang, Wen-Jie Zhang, Lei Liu, Xiao-Xue Du, Yu Han
The human EGFR family consists of four type-1 transmembrane tyrosine kinase receptors: HER1 (EGFR, ErbB1), HER2 (Neu, ErbB2), HER3 (ErbB3), and HER4 (ErbB4). HER3 can dimerize with EGFR, HER2 and even c-Met and likely plays a central role in the response to EGFR-targeted therapy. Because HER3 lacks significant kinase activity and cannot be inhibited by tyrosine kinase inhibitors, neutralizing antibodies and alternative inhibitors of HER3 have been sought as cancer therapeutics. Here, we describe the stable suppression of HER3 mRNA and protein using siRNA...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28868121/melatonin-upregulates-erbb1-and-erbb4-two-primary-implantation-receptors-in-pre-implantation-mouse-embryos
#19
Ghazaleh Moshkdanian, Fatemeh Moghani-Ghoroghi, Parichehr Pasbakhsh, Seyed Noureddin Nematollahi-Mahani, Atefeh Najafi, sIraj Ragerdi Kashani
OBJECTIVES: To evaluated the effects of melatonin on early embryo competence and the expression rate of the primary implantation receptors (ErbB1 and ErbB4). MATERIALS AND METHODS: Two-cell mouse embryos were cultured in 3 groups: simple media, melatonin-treated (10(-9) M melatonin) and Luzindole-treated (10(-9) M luzindole). Then, the rate of ErbB1 and ErbB4 gene and protein expression, the level of intracellular ROS, antioxidant capacity, and also the number of cells were evaluated and compared with the fourth group in vivo developed blastocysts (control group)...
June 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28828402/neuregulin-and-dopamine-d4-receptors-contribute-independently-to-depotentiation-of-schaffer-collateral-ltp-by-temperoammonic-path-stimulation
#20
Yukitoshi Izumi, Charles F Zorumski
Prior studies have found that dopamine (DA), acting at D4 receptors, and neuregulin (NRG), likely acting at ErbB4 receptors, are involved in a form of depotentiation of long-term potentiation (LTP) at Schaffer collateral (SC) synapses in the hippocampus. Furthermore, DA and NRG actions are intertwined in that NRG induces DA release. We previously found that low-frequency stimulation (LFS) of temperoammonic (TA) inputs to area CA1 also depotentiates previously established SC LTP through a complex signaling pathway involving endocannabinoids, GABA, adenosine, and mitogen-activated protein kinases (MAPKs), but not glutamate...
July 2017: ENeuro
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