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https://www.readbyqxmd.com/read/29042681/the-construction-of-intrahepatic-cholangiocarcinoma-model-in-zebrafish
#1
Jing Wang, Xiaoqian Leng, Guiping Wang, Xiaoyang Wan, Hong Cao
Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumor, difficult to diagnose even at an early stage. In this study, we successfully constructed an nras (61K) -induced ICC model in zebrafish. Transcriptome analysis and gene set enrichment analysis (GSEA) of liver samples of the ICC and WT (wild-type) zebrafish revealed that the genes differentially expressed between the two groups were mainly involved in focal adhesion, chemokine signaling and metabolic pathways. Analysis of DNA methylomes revealed that compared with WT samples, methylated genes in ICC samples were enriched in functions associated with cellular, single-organism and metabolic processes...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28887496/differential-gene-expression-profiling-linked-to-tumor-progression-of-splenic-marginal-zone-lymphoma
#2
Tomonori Higuchi, Yumiko Hashida, Ayuko Taniguchi, Mikio Kamioka, Masanori Daibata
The genetic events that lead to aggressive transformation of cases of splenic marginal zone lymphoma (SMZL) after the chronic clinical stage have not been well understood. We aimed to find candidate genes associated with aggressive features of SMZL. We have successfully established two SMZL cell lines, designated SL-15 and SL-22, derived from the same patient's tumor clone in chronic and aggressive phases, respectively. Microarray analysis identified cell cycle-associated genes-specifically PLK1-as the most significantly upregulated in primary aggressive SMZL cells compared with cells from chronic phase...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28856689/real-time-large-scale-in-vivo-observations-reveal-intrinsic-synchrony-plasticity-and-growth-cone-dynamics-of-midline-crossing-axons-during-neuronal-wiring-of-the-zebrafish-spinal-cord
#3
Søren S L Andersen
How axons are wired in the vertebrate spinal cord has been studied mostly using fixed samples or looking at individually growing axons. Using light-sheet microscopy, early neural development is here followed in vivo in real time at high resolution along several hundred micrometers of the zebrafish spinal cord. The dynamics and time course of cellular development and axonal wiring of interneurons expressing GFP under control of the dmrt3 promotor are analyzed. Following neurulation, commissural axons are observed crossing the ventral floor plate midline perpendicularly at about 20 microns/h and in a manner dependent on the Robo3 but not the EphA4 receptors...
August 30, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28851287/epha-receptors-and-ephrin-a-ligands-are-upregulated-by-monocytic-differentiation-maturation-and-promote-cell-adhesion-and-protrusion-formation-in-hl60-monocytes
#4
Midori Mukai, Norihiko Suruga, Noritaka Saeki, Kazushige Ogawa
BACKGROUND: Eph signaling is known to induce contrasting cell behaviors such as promoting and inhibiting cell adhesion/spreading by altering F-actin organization and influencing integrin activities. We have previously demonstrated that EphA2 stimulation by ephrin-A1 promotes cell adhesion through interaction with integrins and integrin ligands in two monocyte/macrophage cell lines. Although mature mononuclear leukocytes express several members of the EphA/ephrin-A subclass, their expression has not been examined in monocytes undergoing during differentiation and maturation...
August 29, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28816646/chronic-cigarette-smoke-mediated-global-changes-in-lung-mucoepidermoid-cells-a-phosphoproteomic-analysis
#5
Hitendra S Solanki, Jayshree Advani, Aafaque Ahmad Khan, Aneesha Radhakrishnan, Nandini A Sahasrabuddhe, Sneha M Pinto, Xiaofei Chang, Thottethodi Subrahmanya Keshava Prasad, Premendu Prakash Mathur, David Sidransky, Harsha Gowda, Aditi Chatterjee
Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28795314/microrna-335-suppresses-the-proliferation-migration-and-invasion-of-breast-cancer-cells-by-targeting-epha4
#6
Yilong Dong, Yang Liu, Aimei Jiang, Ruiqian Li, Min Yin, Yanmei Wang
MicroRNAs (miRNAs) are small noncoding RNAs that exert their functions by targeting specific mRNA sequences. Many studies have demonstrated that miRNAs are crucial for cancer progression, during which they can act as either oncogenes or tumor suppressors. Previous research has shown that miR-335 is downregulated in breast cancer, and it has been shown to be a breast cancer suppressor. In addition, emerging evidence indicates that erythropoietin-producing hepatocellular A4 (EphA4) is implicated in cancer cell proliferation, migration, and invasion...
August 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28769056/increased-epha4-ephexin1-signaling-in-the-medial-prefrontal-cortex-plays-a-role-in-depression-like-phenotype
#7
Ji-Chun Zhang, Wei Yao, Youge Qu, Mayumi Nakamura, Chao Dong, Chun Yang, Qian Ren, Min Ma, Mei Han, Yukihiko Shirayama, Akiko Hayashi-Takagi, Kenji Hashimoto
Accumulating evidence suggests a role of the ephrin receptor EphA4 and the downstream protein ephexin1 in synaptic plasticity, which is implicated in depression. We examined whether EphA4-ephexin1 signaling plays a role in the pathophysiology of depression, and the antidepressant-like effect of EphA4 inhibitor rhynchophylline. We found increased ratios of p-EphA4/EphA4 and p-ephexin1/ephexin1 in the prefrontal cortex (PFC) and hippocampus but not in the nucleus accumbens (NAc), of susceptible mice after social defeat stress...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28753740/photopolymerized-micropatterns-with-high-feature-frequencies-overcome-chemorepulsive-borders-to-direct-neurite-growth
#8
Bradley W Tuft, Linjing Xu, Braden Leigh, Daniel Lee, C Allan Guymon, Marlan R Hansen
Developing and regenerating neurites respond to a variety of biophysical and biochemical cues in their microenvironment to reach target cells and establish appropriate synapses. Defining the hierarchal relationship of both types of cues to direct neurite growth carries broad significance for neural development, regeneration, and, in particular, engineering of neural prostheses that improve tissue integration with native neural networks. In this work, chemorepulsive biochemical borders are established on substrates with a range of surface microfeatures to determine the potential of physical cues to overcome conflicting biochemical cues...
July 28, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28747680/glycoengineering-of-epha4-fc-leads-to-a-unique-long-acting-and-broad-spectrum-eph-receptor-therapeutic-antagonist
#9
Cassandra L Pegg, Leanne T Cooper, Jing Zhao, Michael Gerometta, Fiona M Smith, Michael Yeh, Perry F Bartlett, Jeffrey J Gorman, Andrew W Boyd
Eph receptors have emerged as targets for therapy in both neoplastic and non-neoplastic disease, however, particularly in non-neoplastic diseases, redundancy of function limits the effectiveness of targeting individual Eph proteins. We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist. However, a very short in vivo half-life effectively limited its therapeutic development...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747385/spinal-racgap-%C3%AE-chimaerin-is-required-to-establish-the-midline-barrier-for-proper-corticospinal-axon-guidance
#10
Shota Katori, Yukiko Noguchi-Katori, Shigeyoshi Itohara, Takuji Iwasato
In the developing CNS, the midline barrier, which comprises guidance molecule-expressing midline glial somata and processes, plays a pivotal role in midline axon guidance. Accumulating evidence has revealed the molecular mechanisms by which the midline barrier ensures proper midline guidance for axons. In contrast, the mechanisms for establishing the midline barrier remain obscure. Here, we report that Rac-specific GTPase-activating protein (RacGAP) α-chimaerin is required for both axonal repulsion at and establishment of the midline barrier in the spinal cord...
August 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28698029/critical-role-of-epha4-in-early-brain-injury-after-subarachnoid-hemorrhage-in-rat
#11
Ruiming Fan, Budbazar Enkhjargal, Richard Camara, Feng Yan, Lei Gong, ShengtaoYao, Jiping Tang, Yangmei Chen, John H Zhang
Early brain injury (EBI) is reported as a primary cause of mortality in subarachnoid hemorrhage (SAH) patients. Eph receptor A4 (EphA4) has been associated with blood-brain barrier integrity and pro-apoptosis. We aimed to investigate a role of EphA4 in EBI after SAH. One hundred and seventy-nine male adult Sprague-Dawley rats were randomly divided into sham versus endovascular perforation model of SAH groups. SAH grade, neurological score, Evans blue dye extravasation, brain water content, mortality, Fluoro-Jade staining, immunofluorescence staining, and western blot experiments were performed after SAH...
October 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28687613/valproic-acid-induces-aberrant-development-of-striatal-compartments-and-corticostriatal-pathways-in-a-mouse-model-of-autism-spectrum-disorder
#12
Hsiao-Ying Kuo, Fu-Chin Liu
The striatum comprises two neurochemical compartments: striosomes and the matrix. Striosomal and matrix compartments receive inputs from limbic system-related and sensorimotor cortices, respectively. Here, we investigate the impact on the corticostriosomal pathway in the valproic acid (VPA)-induced autism spectrum disorder mouse model. VPA administration during the neurogenesis time windows of striosomes, but not the matrix, resulted in aberrant compartmentation [i.e., maternal VPA injections at embryonic day (E)12...
October 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28686668/molecular-interactions-of-epha4-growth-hormone-receptor-janus-kinase-2-and-signal-transducer-and-activator-of-transcription-5b
#13
Takahiro Sawada, Daiki Arai, Xuefeng Jing, Masayasu Miyajima, Stuart J Frank, Kazushige Sakaguchi
We previously reported that EphA4, a member of the Eph family of receptor tyrosine kinases, is an important modulator of growth hormone (GH) signaling, leading to augmented synthesis of insulin-like growth factor 1 (IGF1) for postnatal body growth. In the present study, we report the molecular interactions of EphA4, GH receptor (GHR), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 5B (STAT5B). EphA4 binds to GHR at both its extracellular and intracellular domains and phosphorylates GHR when stimulated with a ligand...
2017: PloS One
https://www.readbyqxmd.com/read/28660300/cell-type-specific-localization-of-ephs-pairing-with-ephrin-b2-in-the-rat-postnatal-pituitary-gland
#14
Saishu Yoshida, Takako Kato, Naoko Kanno, Naoto Nishimura, Hiroto Nishihara, Kotaro Horiguchi, Yukio Kato
Sox2-expressing stem/progenitor cells in the anterior lobe of the pituitary gland form two types of micro-environments (niches): the marginal cell layer and dense cell clusters in the parenchyma. In relation to the mechanism of regulation of niches, juxtacrine signaling via ephrin and its receptor Eph is known to play important roles in various niches. The ephrin and Eph families are divided into two subclasses to create ephrin/Eph signaling in co-operation with confined partners. Recently, we reported that ephrin-B2 localizes specifically to both pituitary niches...
June 28, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28529623/high-expression-of-epha4-predicted-lesser-degree-of-tumor-regression-after-neoadjuvant-chemoradiotherapy-in-rectal-cancer
#15
Ching-Yih Lin, Ying-En Lee, Yu-Feng Tian, Ding-Ping Sun, Ming-Jen Sheu, Chen-Yi Lin, Chien-Feng Li, Sung-Wei Lee, Li-Ching Lin, I-Wei Chang, Chieh-Tien Wang, Hong-Lin He
Background: Numerous transmembrane receptor tyrosine kinase pathways have been found to play an important role in tumor progression in some cancers. This study was aimed to evaluate the clinical impact of Eph receptor A4 (EphA4) in patients with rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT) combined with mesorectal excision, with special emphasis on tumor regression. Methods: Analysis of the publicly available expression profiling dataset of rectal cancer disclosed that EphA4 was the top-ranking, significantly upregulated, transmembrane receptor tyrosine kinase pathway-associated gene in the non-responders to CCRT, compared with the responders...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28526745/identification-and-characterization-of-nanobodies-targeting-the-epha4-receptor
#16
Lies Schoonaert, Laura Rué, Bart Roucourt, Mieke Timmers, Susan Little, Lucía Chávez-Gutiérrez, Maarten Dewilde, Peter Joyce, Adam Curnock, Peter Weber, Jurgen Haustraete, Gholamreza Hassanzadeh-Ghassabeh, Bart De Strooper, Ludo Van Den Bosch, Philip Van Damme, Robin Lemmens, Wim Robberecht
The ephrin receptor A4 (EphA4) is one of the receptors in the ephrin system that plays a pivotal role in a variety of cell-cell interactions, mostly studied during development. In addition, EphA4 has been found to play a role in cancer biology as well as in the pathogenesis of several neurological disorders such as stroke, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease. Pharmacological blocking of EphA4 has been suggested to be a therapeutic strategy for these disorders...
July 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28491025/change-of-rin1-and-stathmin-in-the-animal-model-of-traumatic-stresses
#17
Fang Han, Jingzhi Jiang, Jinlan Ding, Hong Liu, Bing Xiao, Yuxiu Shi
The molecular mechanism of fear memory is poorly understood. Therefore, the pathogenesis of post-traumatic stress disorder (PTSD), whose symptom presentation can enhance fear memory, remains largely unclear. Recent studies with knockout animals have reported that Rin1 and stathmin regulate fear memory. Rin1 inhibits acquisition and promotes memory extinction, whereas stathmin regulates innate and basal fear. The aim of our study was to examine changes in the expression of Rin1 and stathmin in different animal models of stress, particluarly traumatic stress...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28488395/shorter-duration-of-non-rapid-eye-movement-sleep-slow-waves-in-epha4-knockout-mice
#18
Marlène Freyburger, Gaétan Poirier, Julie Carrier, Valérie Mongrain
Slow waves occurring during non-rapid eye movement sleep have been associated with neurobehavioural performance and memory. In addition, the duration of previous wakefulness and sleep impacts characteristics of these slow waves. However, molecular mechanisms regulating the dynamics of slow-wave characteristics remain poorly understood. The EphA4 receptor regulates glutamatergic transmission and synaptic plasticity, which have both been linked to sleep slow waves. To investigate if EphA4 regulates slow-wave characteristics during non-rapid eye movement sleep, we compared individual parameters of slow waves between EphA4 knockout mice and wild-type littermates under baseline conditions and after a 6-h sleep deprivation...
October 2017: Journal of Sleep Research
https://www.readbyqxmd.com/read/28425198/the-cell-adhesion-molecule-epha4-is-involved-in-circadian-clock-functions
#19
Silke Kiessling, Emma K O'Callaghan, Marlène Freyburger, Nicolas Cermakian, Valérie Mongrain
Circadian (~24 h) rhythms of cellular network plasticity in the central circadian clock, the suprachiasmatic nucleus (SCN), have been described. The neuronal network in the SCN regulates photic resetting of the circadian clock as well as stability of the circadian system during both entrained and constant conditions. EphA4, a cell adhesion molecule regulating synaptic plasticity by controlling connections of neurons and astrocytes, is expressed in the SCN. To address whether EphA4 plays a role in circadian photoreception and influences the neuronal network of the SCN, we have analysed circadian wheel-running behavior of EphA4 knockout (EphA4(-/-) ) mice under different light conditions and upon photic resetting, as well as their light-induced protein response in the SCN...
April 20, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28424425/ephrin-b3-supports-glioblastoma-growth-by-inhibiting-apoptosis-induced-by-the-dependence-receptor-epha4
#20
Amélie Royet, Laura Broutier, Marie-May Coissieux, Céline Malleval, Nicolas Gadot, Denis Maillet, Lise Gratadou-Hupon, Agnès Bernet, Pascale Nony, Isabelle Treilleux, Jérôme Honnorat, Daniel Liebl, Laurent Pelletier, François Berger, David Meyronet, Marie Castets, Patrick Mehlen
EphA4, an Ephrins tyrosine kinase receptor, behaves as a dependence receptor (DR) by triggering cell apoptosis in the absence of its ligand Ephrin-B3. DRs act as conditional tumor suppressors, engaging cell death based on ligand availability; this mechanism is bypassed by overexpression of DRs ligands in some aggressive cancers. The pair EphA4/Ephrin-B3 favors survival of neuronal progenitors of the brain subventricular zone, an area where glioblastoma multiform (GBM) are thought to originate. Here, we report that Ephrin-B3 is highly expressed in human biopsies and that it inhibits EphA4 pro-apoptotic activity in tumor cells...
March 10, 2017: Oncotarget
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