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Neuregulin

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https://www.readbyqxmd.com/read/28796387/ulinastatin-inhibited-sepsis-induced-spinal-inflammation-to-alleviate-peripheral-neuromuscular-dysfunction-in-an-experimental-rat-model-of-neuromyopathy
#1
Fei Xie, Su Min, Jingyuan Chen, Jun Yang, Xin Wang
Sepsis initiates a neuroinflammatory cascade that contributes to spinal cord inflammation and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of this cascade. In this study, we tested the hypothesis that ulinastatin (ULI) inhibits sepsis-induced spinal inflammation to alleviate peripheral neuromuscular dysfunction through the TLR4/MyD88/NF-κB signaling pathway. Muscular function, spinal cord water content, and cytokine levels of spinal cord were tested in TLR4-inhibited rats subjected to cecal ligation and puncture (CLP)...
August 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28796037/functional-prediction-of-mir-3144-5p-in-human-cardiac-myocytes-based-on-transcriptome-sequencing-and-bioinformatics
#2
Lei Ruan, Yi Yang, Yi Huang, Ling Ding, Cuntai Zhang, Xiaofen Wu
BACKGROUND: RAN guanine nucleotide release factor (RANGRF) encoding protein MOG1 plays an important role in cardiac arrhythmia, so we intended to investigate the regulatory miRNA of RANGRF and explore its potential regulatory mechanism in arrhythmogenesis. METHODS: Based on bioinformatic analysis, miR-3144-5p was predicted to be a regulatory miRNA of RANGRF, which were then validated through a dual-luciferase reporter plasmid assay. Subsequently, the expression level of miR-3144-5p in human cardiac myocytes (HCMs) was detected, followed by cell transfection with miR-3144-5p mimics...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28792672/constitutive-loss-and-acute-pharmacological-manipulation-of-erbb4-signaling-do-not-affect-attention-and-inhibitory-control-in-mice
#3
Elena Marchisella, Ruud Wijnands, Bastijn Koopmans, Sabine Spijker, Maarten Loos
The receptor tyrosine kinase ErbB4 and its ligand trophic factors of the neuregulin (NRG) family have been associated with schizophrenia and other mental disorders in human genetic studies. In vivo studies in mice have shown how abnormal Nrg-ErbB4 signaling leads to deviant behaviors relevant to distinct aspects of schizophrenia, including hyperactivity, sensory gating deficits, working and spatial memory deficits and impaired social behavior. However, so far little is known on the role of ErbB4 in attention and inhibitory control, two aspects of executive functions that are impaired in schizophrenia...
August 9, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28781988/multiple-response-regression-analysis-links-magnetic-resonance-imaging-features-to-de-regulated-protein-expression-and-pathway-activity-in-lower-grade-glioma
#4
Michael Lehrer, Anindya Bhadra, Visweswaran Ravikumar, James Y Chen, Max Wintermark, Scott N Hwang, Chad A Holder, Erich P Huang, Brenda Fevrier-Sullivan, John B Freymann, Arvind Rao
BACKGROUND AND PURPOSE: Lower grade gliomas (LGGs), lesions of WHO grades II and III, comprise 10-15% of primary brain tumors. In this first-of-a-kind study, we aim to carry out a radioproteomic characterization of LGGs using proteomics data from the TCGA and imaging data from the TCIA cohorts, to obtain an association between tumor MRI characteristics and protein measurements. The availability of linked imaging and molecular data permits the assessment of relationships between tumor genomic/proteomic measurements with phenotypic features...
May 2017: Oncoscience
https://www.readbyqxmd.com/read/28780372/species-specific-effects-of-neuregulin-1%C3%AE-cimaglermin-alfa-on-glucose-handling-in-animal-models-and-humans-with-heart-failure
#5
Zhihong Huang, Douglas B Sawyer, Erika L Troy, Corissa McEwen, John H Cleator, Abigail Murphy, Anthony O Caggiano, Andrew Eisen, Tom J Parry
Neuregulin-1β is a member of the neuregulin family of growth factors and is critically important for normal development and functioning of the heart and brain. A recombinant version of neuregulin-1β, cimaglermin alfa (also known as glial growth factor 2 or GGF2) is being investigated as a possible therapy for heart failure. Previous studies suggest that neuregulin-1β stimulation of skeletal muscle increases glucose uptake and, specifically, sufficient doses of cimaglermin alfa acutely produce hypoglycemia in pigs...
August 2, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28756200/erbb4-protects-against-neuronal-apoptosis-via-activation-of-yap-pik3cb-signaling-pathway-in-a-rat-model-of-subarachnoid-hemorrhage
#6
Feng Yan, Xiaoxiao Tan, Weifeng Wan, Brandon J Dixon, Ruiming Fan, Budbazar Enkhjargal, Qian Li, Jianmin Zhang, Gao Chen, John H Zhang
Neuronal apoptosis is a central pathological process in subarachnoid hemorrhage (SAH)-induced early brain injury. Previous studies indicated that ErbB4 (EGFR family member v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) is essential for normal development and maintenance of the nervous system. In this study, we explored the neuroprotective effects of ErbB4 and its downstream YAP (yes-associated protein)/PIK3CB signaling pathway in early brain injury after SAH in a rat model using the endovascular perforation method...
July 27, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28752050/nrg4-promotes-fuel-oxidation-and-a-healthy-adipokine-profile-to-ameliorate-diet-induced-metabolic-disorders
#7
Zhimin Chen, Guo-Xiao Wang, Sara L Ma, Dae Young Jung, Hyekyung Ha, Tariq Altamimi, Xu-Yun Zhao, Liang Guo, Peng Zhang, Chun-Rui Hu, Ji-Xin Cheng, Gary D Lopaschuk, Jason K Kim, Jiandie D Lin
OBJECTIVE: Brown and white adipose tissue exerts pleiotropic effects on systemic energy metabolism in part by releasing endocrine factors. Neuregulin 4 (Nrg4) was recently identified as a brown fat-enriched secreted factor that ameliorates diet-induced metabolic disorders, including insulin resistance and hepatic steatosis. However, the physiological mechanisms through which Nrg4 regulates energy balance and glucose and lipid metabolism remain incompletely understood. The aims of the current study were: i) to investigate the regulation of adipose Nrg4 expression during obesity and the physiological signals involved, ii) to elucidate the mechanisms underlying Nrg4 regulation of energy balance and glucose and lipid metabolism, and iii) to explore whether Nrg4 regulates adipose tissue secretome gene expression and adipokine secretion...
August 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28732471/gene-expression-patterns-of-chicken-neuregulin-3-in-association-with-copy-number-variation-and-frameshift-deletion
#8
Hideaki Abe, Daiki Aoya, Hiro-Aki Takeuchi, Miho Inoue-Murayama
BACKGROUND: Neuregulin 3 (NRG3) plays a key role in central nervous system development and is a strong candidate for human mental disorders. Thus, genetic variation in NRG3 may have some impact on a variety of phenotypes in non-mammalian vertebrates. Recently, genome-wide screening for short insertions and deletions in chicken (Gallus gallus) genomes has provided useful information about structural variation in functionally important genes. NRG3 is one such gene that has a putative frameshift deletion in exon 2, resulting in premature termination of translation...
July 21, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28729842/a-gene-based-analysis-of-acoustic-startle-latency
#9
Alicia K Smith, Tanja Jovanovic, Varun Kilaru, Adriana Lori, Lauren Gensler, Samuel S Lee, Seth Davin Norrholm, Nicholas Massa, Bruce Cuthbert, Bekh Bradley, Kerry J Ressler, Erica Duncan
Latency of the acoustic startle response is the time required from the presentation of startling auditory stimulus until the startle response is elicited and provides an index of neural processing speed. Latency is prolonged in subjects with schizophrenia compared to controls in some but not all studies and is 68-90% heritable in baseline startle trials. In order to determine the genetic association with latency as a potential inroad into genetically based vulnerability to psychosis, we conducted a gene-based study of latency followed by an independent replication study of significant gene findings with a single-nucleotide polymorphism (SNP)-based analysis of schizophrenia and control subjects...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28727685/erbb4-signaling-in-dopaminergic-axonal-projections-increases-extracellular-dopamine-levels-and-regulates-spatial-working-memory-behaviors
#10
M Skirzewski, I Karavanova, A Shamir, L Erben, J Garcia-Olivares, J H Shin, D Vullhorst, V A Alvarez, S G Amara, A Buonanno
Genetic variants of Neuregulin 1 (NRG1) and its neuronal tyrosine kinase receptor ErbB4 are associated with risk for schizophrenia, a neurodevelopmental disorder characterized by excitatory/inhibitory imbalance and dopamine (DA) dysfunction. To date, most ErbB4 studies have focused on GABAergic interneurons in the hippocampus and neocortex, particularly fast-spiking parvalbumin-positive (PV+) basket cells. However, NRG has also been shown to modulate DA levels, suggesting a role for ErbB4 signaling in dopaminergic neuron function...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28723928/erbb-activation-signatures-as-potential-biomarkers-for-anti-erbb3-treatment-in-hnscc
#11
Diego Alvarado, Gwenda F Ligon, Jay S Lillquist, Scott B Seibel, Gerald Wallweber, Veronique M Neumeister, David L Rimm, Gerald McMahon, Theresa M LaVallee
Head and neck squamous cell carcinoma (HNSCC) accounts for 3-5% of all tumor types and remains an unmet medical need with only two targeted therapies approved to date. ErbB3 (HER3), the kinase-impaired member of the EGFR/ErbB family, has been implicated as a disease driver in a number of solid tumors, including a subset of HNSCC. Here we show that the molecular components required for ErbB3 activation, including its ligand neuregulin-1 (NRG1), are highly prevalent in HNSCC and that HER2, but not EGFR, is the major activating ErbB3 kinase partner...
2017: PloS One
https://www.readbyqxmd.com/read/28722233/cooperative-interaction-of-hepatocyte-growth-factor-and-neuregulin-regulates-schwann-cell-migration-and-proliferation-through-grb2-associated-binder-2-in-peripheral-nerve-repair
#12
Yoon Kyoung Shin, So Young Jang, Seoug Hoon Yun, Yun Young Choi, Byeol-A Yoon, Young Rae Jo, So Young Park, Min Gyoung Pak, Joo In Park, Hwan Tae Park
The sequential reactive changes in Schwann cell phenotypes in transected peripheral nerves, including dedifferentiation, proliferation and migration, are essential for nerve repair. Even though the injury-induced migratory and proliferative behaviors of Schwann cells resemble epithelial and mesenchymal transition (EMT) in tumors, the molecular mechanisms underlying this phenotypic change of Schwann cells are still unclear. Here we show that the reactive Schwann cells exhibit migratory features dependent on the expression of a scaffolding oncoprotein Grb2-associated binder-2 (Gab2), which was transcriptionally induced by neuregulin 1-ErbB2 signaling following nerve injury...
July 19, 2017: Glia
https://www.readbyqxmd.com/read/28709749/the-brown-fat-secreted-adipokine-neuregulin-4-is-decreased-in-gestational-diabetes-mellitus
#13
S Kralisch, A Hoffmann, J Kratzsch, M Blüher, M Stumvoll, M Fasshauer, T Ebert
AIMS: Neuregulin 4 has recently been recognized as a novel adipokine secreted by brown adipose tissue (BAT), with beneficial effects on murine insulin resistance and hepatic steatosis. Yet, thus far, neither regulation of neuregulin 4 in gestational diabetes mellitus (GDM) nor its longitudinal changes in the peripartum period have been elucidated. METHODS: Circulating neuregulin 4 levels were measured by ELISA in 74 women with GDM and 74 healthy, gestational-age-matched controls...
July 11, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28698179/a-novel-regulatory-mechanism-of-smooth-muscle-%C3%AE-actin-expression-by-nrg-1-circacta2-mir-548f-5p-axis
#14
Yan Sun, Zhan Yang, Bin Zheng, Xin-Hua Zhang, Man-Li Zhang, Xue-Shan Zhao, Hong-Ye Zhao, Toru Suzuki, Jin-Kun Wen
Rationale: Neuregulin-1 (NRG-1) includes an extracellular EGF-like domain and an intracellular domain (NRG-1-ICD). In response to transforming growth factor (TGF)-β1,its cleavage by proteolytic enzymes releases a bioactive fragment, which suppresses the vascular smooth muscle cell (VSMC) proliferation by activating ErbB receptor. However, NRG-1-ICD function in VSMCs remains unknown. Objective: Here, we characterize the function of NRG-1-ICD and underlying mechanisms in VSMCs. Methods and Results: Immunofluorescence staining, Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) showed that NRG-1 was expressed in rat, mouse and human VSMCs and was upregulated and cleaved in response to TGF-β1...
July 11, 2017: Circulation Research
https://www.readbyqxmd.com/read/28689005/neuregulin-1%C3%AE-as-a-potential-therapeutic-for-targeting-fibroblasts-in-heart-disease
#15
EDITORIAL
Jason D Gardner
No abstract text is available yet for this article.
July 5, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28683304/inhibition-of-the-schizophrenia-associated-microrna-mir-137-disrupts-nrg1%C3%AE-neurodevelopmental-signal-transduction
#16
Kristen Therese Thomas, Bart Russell Anderson, Niraj Shah, Stephanie Elaine Zimmer, Daniel Hawkins, Arielle Nicole Valdez, Qiaochu Gu, Gary Jonathan Bassell
Genomic studies have repeatedly associated variants in the gene encoding the microRNA miR-137 with increased schizophrenia risk. Bioinformatic predictions suggest that miR-137 regulates schizophrenia-associated signaling pathways critical to neural development, but these predictions remain largely unvalidated. In the present study, we demonstrate that miR-137 regulates neuronal levels of p55γ, PTEN, Akt2, GSK3β, mTOR, and rictor. All are key proteins within the PI3K-Akt-mTOR pathway and act downstream of neuregulin (Nrg)/ErbB and BDNF signaling...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28680299/the-scaffolding-protein-grb2-associated-binder-1-in-skeletal-muscles-and-terminal-schwann-cells-regulates-postnatal-neuromuscular-synapse-maturation
#17
So Young Park, So Young Jang, Yoon Kyoung Shin, Dong Keun Jung, Byeol A Yoon, Jong Kook Kim, Young Rae Jo, Hye Jeong Lee, Hwan Tae Park
The vertebrate neuromuscular junction (NMJ) is considered as a "tripartite synapse" consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice...
June 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28675393/erbb4-signaling-in-the-prelimbic-cortex-regulates-fear-expression
#18
Y-H Chen, Y-J Lan, S-R Zhang, W-P Li, Z-Y Luo, S Lin, J-P Zhuang, X-W Li, S-J Li, J-M Yang, T-M Gao
Many psychiatric diseases such as post-traumatic stress disorder (PTSD) are characterized by abnormal processing of emotional stimuli particularly fear. The medial prefrontal cortex (mPFC) is critically involved in fear expression. However, the molecular mechanisms underlying this process are largely unknown. Neuregulin-1 (NRG1) reportedly regulates pyramidal neuronal activity via ErbB4 receptors, which are abundant in parvalbumin (PV)-expressing interneurons in the PFC. In this study, we aimed to determine how NRG1/ErbB4 signaling in the mPFC modulates fear expression and found that tone-cued fear conditioning increased NRG1 expression in the mPFC...
July 4, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28675388/disrupted-hippocampal-neuregulin-1-erbb3-signaling-and-dentate-gyrus-granule-cell-alterations-in-suicide
#19
I Mahar, B Labonte, S Yogendran, E Isingrini, L Perret, M A Davoli, A Rachalski, B Giros, G Turecki, N Mechawar
Neuregulin-1 (NRG1) and ErbB receptors have been associated with psychopathology, and NRG1-ErbB3 signaling has been shown to increase hippocampal neurogenesis and induce antidepressant-like effects. In this study, we aimed to determine whether deficits in NRG1 or ErbBs might be present in the hippocampus of suicide completers. In well-characterized postmortem hippocampal samples from suicides and matched sudden-death controls, we assessed gene expression and methylation using qRT-PCR and EpiTYPER, respectively...
July 4, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28668379/design-and-optimization-of-plga-microparticles-for-controlled-and-local-delivery-of-neuregulin-1-in-traumatic-spinal-cord-injury
#20
Kallivalappil T Santhosh, Arsalan Alizadeh, Soheila Karimi-Abdolrezaee
Spinal cord injury (SCI) results in significant tissue damage that underlies functional impairments. Pharmacological interventions to confer neuroprotection and promote cell replacement are essential for SCI repair. We previously reported that Neuregulin-1 (Nrg-1) is acutely and permanently downregulated after SCI. Nrg-1 is a critical growth factor for differentiation of neural precursor cells (NPCs) into myelinating oligodendrocytes. We showed that intrathecal delivery of Nrg-1 enhances oligodendrocyte replacement following SCI...
September 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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