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EdnrB pathway

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https://www.readbyqxmd.com/read/27881779/allergic-inflammation-leads-to-neuropathic-pain-via-glial-cell-activation
#1
Ryo Yamasaki, Takayuki Fujii, Bing Wang, Katsuhisa Masaki, Mizuho A Kido, Mari Yoshida, Takuya Matsushita, Jun-Ichi Kira
: Allergic and atopic disorders have increased over the past few decades and have been associated with neuropsychiatric conditions, such as autism spectrum disorder and asthmatic amyotrophy. Myelitis presenting with neuropathic pain can occur in patients with atopic disorder; however, the relationship between allergic inflammation and neuropathic pain, and the underlying mechanism, remains to be established. We studied whether allergic inflammation affects the spinal nociceptive system...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27863272/genome-wide-analysis-of-aberrant-gene-expression-and-methylation-profiles-reveals-susceptibility-genes-and-underlying-mechanism-of-cervical-cancer
#2
Hongmei Lin, Yifei Ma, Yongqing Wei, Hui Shang
BACKGROUND: This study aimed to explore the molecular mechanism of cervical cancer (CC) by integrated bioinformatic analyses of gene expression and methylation profiles. METHODS: The gene expression and methylation microarrays in CC samples and normal controls were respectively downloaded from the GEO database. After screening the differentially expressed genes (DEGs) with Limma package and the CC-related methylation sites with CpGassoc package in R language, DEGs with CC-related methylation sites were identified from the intersection of the above two groups of results with 50kb upstream and downstream of a gene as the gene region...
October 26, 2016: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/27270507/genetic-variations-associated-with-six-white-point-coat-pigmentation-in-diannan-small-ear-pigs
#3
Meng-Die Lü, Xu-Man Han, Yun-Fei Ma, David M Irwin, Yun Gao, Jia-Kun Deng, Adeniyi C Adeola, Hai-Bing Xie, Ya-Ping Zhang
A common phenotypic difference among domestic animals is variation in coat color. Six-white-point is a pigmentation pattern observed in varying pig breeds, which seems to have evolved through several different mechanistic pathways. Herein, we re-sequenced whole genomes of 31 Diannan small-ear pigs from China and found that the six-white-point coat color in Diannan small-ear pigs is likely regulated by polygenic loci, rather than by the MC1R locus. Strong associations were observed at three loci (EDNRB, CNTLN, and PINK1), which explain about 20 percent of the total coat color variance in the Diannan small-ear pigs...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27200419/insulin-decreases-atherosclerosis-by-inducing-endothelin-receptor-b-expression
#4
Kyoungmin Park, Akira Mima, Qian Li, Christian Rask-Madsen, Pingnian He, Koji Mizutani, Sayaka Katagiri, Yasutaka Maeda, I-Hsien Wu, Mogher Khamaisi, Simone Rordam Preil, Ernesto Maddaloni, Ditte Sørensen, Lars Melholt Rasmussen, Paul L Huang, George L King
Endothelial cell (EC) insulin resistance and dysfunction, caused by diabetes, accelerates atherosclerosis. It is unknown whether specifically enhancing EC-targeted insulin action can decrease atherosclerosis in diabetes. Accordingly, overexpressing insulin receptor substrate-1 (IRS1) in the endothelia of Apoe(-/-) mice (Irs1/Apoe(-/-)) increased insulin signaling and function in the aorta. Atherosclerosis was significantly reduced in Irs1/ApoE(-/-) mice on diet-induced hyperinsulinemia and hyperglycemia. The mechanism of insulin's enhanced antiatherogenic actions in EC was related to remarkable induction of NO action, which increases endothelin receptor B (EDNRB) expression and intracellular [Ca(2+)]...
May 5, 2016: JCI Insight
https://www.readbyqxmd.com/read/27148356/gnaq-and-gna11-in-the-endothelin-signaling-pathway-and-melanoma
#5
Oscar Urtatiz, Catherine D Van Raamsdonk
In this article, we first briefly outline the function of G protein coupled receptors in cancer, and then specifically examine the roles of the seven transmembrane G protein coupled Endothelin B receptor (Ednrb) and the G proteins, GNAQ and GNA11, in both melanocyte development and melanoma. Ednrb plays an essential role in melanocyte development. GNAQ and GNA11 are oncogenes when mutated in certain types of melanocytic lesions, being extremely frequent in uveal melanoma, which forms from melanocytes located in the eye...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27134165/ednrb-governs-regenerative-response-of-melanocyte-stem-cells-by-crosstalk-with-wnt-signaling
#6
Makoto Takeo, Wendy Lee, Piul Rabbani, Qi Sun, Hai Hu, Chae Ho Lim, Prashiela Manga, Mayumi Ito
Delineating the crosstalk between distinct signaling pathways is key to understanding the diverse and dynamic responses of adult stem cells during tissue regeneration. Here, we demonstrate that the Edn/EdnrB signaling pathway can interact with other signaling pathways to elicit distinct stem cell functions during tissue regeneration. EdnrB signaling promotes proliferation and differentiation of melanocyte stem cells (McSCs), dramatically enhancing the regeneration of hair and epidermal melanocytes. This effect is dependent upon active Wnt signaling that is initiated by Wnt ligand secretion from the hair follicle epithelial niche...
May 10, 2016: Cell Reports
https://www.readbyqxmd.com/read/26628380/endothelin-b-receptor-activation-in-astrocytes-regulates-the-rate-of-oligodendrocyte-regeneration-during-remyelination
#7
Timothy R Hammond, Brian McEllin, Paul D Morton, Matthew Raymond, Jeff Dupree, Vittorio Gallo
Reactive astrogliosis is an essential and ubiquitous response to CNS injury, but in some cases, aberrant activation of astrocytes and their release of inhibitory signaling molecules can impair endogenous neural repair processes. Our lab previously identified a secreted intercellular signaling molecule, called endothelin-1 (ET-1), which is expressed at high levels by reactive astrocytes in multiple sclerosis (MS) lesions and limits repair by delaying oligodendrocyte progenitor cell (OPC) maturation. However, as ET receptors are widely expressed on neural cells, the cell- and receptor-specific mechanisms of OPC inhibition by ET-1 action remain undefined...
December 15, 2015: Cell Reports
https://www.readbyqxmd.com/read/26276426/rho-kinase-expression-in-hirschsprung-s-disease
#8
David Coyle, Anne Marie O'Donnell, Nicolae Corcionivoschi, John Gillick, Prem Puri
BACKGROUND: Rho-kinase (ROCK) is the primary effector protein in the RhoA pathway, which regulates Ca(2+)-independent smooth muscle contraction in the human bowel. This pathway has been reported to be hyper-activated in the aganglionic bowel of EDNRB-null (-/-) rats compared to the ganglionic bowel from EDNRB (+/+) rats. We hypothesised that ROCK expression is up-regulated in human aganglionic bowel and designed this study to investigate ROCK 1 and ROCK 2 expression in Hirschsprung's disease (HSCR) and controls...
November 2015: Pediatric Surgery International
https://www.readbyqxmd.com/read/26061883/impaired-cellular-immunity-in-the-murine-neural-crest-conditional-deletion-of-endothelin-receptor-b-model-of-hirschsprung-s-disease
#9
Ankush Gosain, Amanda J Barlow-Anacker, Chris S Erickson, Joseph F Pierre, Aaron F Heneghan, Miles L Epstein, Kenneth A Kudsk
Hirschsprung's disease (HSCR) is characterized by aganglionosis from failure of neural crest cell (NCC) migration to the distal hindgut. Up to 40% of HSCR patients suffer Hirschsprung's-associated enterocolitis (HAEC), with an incidence that is unchanged from the pre-operative to the post-operative state. Recent reports indicate that signaling pathways involved in NCC migration may also be involved in the development of secondary lymphoid organs. We hypothesize that gastrointestinal (GI) mucosal immune defects occur in HSCR that may contribute to enterocolitis...
2015: PloS One
https://www.readbyqxmd.com/read/26030901/uvb-stimulates-the-expression-of-endothelin-b-receptor-in-human-melanocytes-via-a-sequential-activation-of-the-p38-msk1-creb-mitf-pathway-which-can-be-interrupted-by-a-french-maritime-pine-bark-extract-through-a-direct-inactivation-of-msk1
#10
Hideki Tagashira, Aki Miyamoto, Sei-Ichi Kitamura, Masahito Tsubata, Kazuya Yamaguchi, Kinya Takagaki, Genji Imokawa
Melanogenesis is the physiological process by which melanin is synthesized to protect the skin from UV damage. While paracrine interactions between keratinocytes and melanocytes are crucial for regulating epidermal pigmentation, the endothelin (EDN)-endothelin B-receptor (EDNRB) interaction is one of the key linkages. In this study, we found that a single exposure of normal human melanocytes (NHMs) with UVB stimulates the expression of EDNRB and its upstream transcription factor microphthalmia-associated transcription factor (MITF) at the transcriptional and translational levels...
2015: PloS One
https://www.readbyqxmd.com/read/25786024/male-biased-aganglionic-megacolon-in-the-tasht-mouse-line-due-to-perturbation-of-silencer-elements-in-a-large-gene-desert-of-chromosome-10
#11
Karl-F Bergeron, Tatiana Cardinal, Aboubacrine M Touré, Mélanie Béland, Diana L Raiwet, David W Silversides, Nicolas Pilon
Neural crest cells (NCC) are a transient migratory cell population that generates diverse cell types such as neurons and glia of the enteric nervous system (ENS). Via an insertional mutation screen for loci affecting NCC development in mice, we identified one line-named TashT-that displays a partially penetrant aganglionic megacolon phenotype in a strong male-biased manner. Interestingly, this phenotype is highly reminiscent of human Hirschsprung's disease, a neurocristopathy with a still unexplained male sex bias...
March 2015: PLoS Genetics
https://www.readbyqxmd.com/read/25546127/endothelin2-induces-expression-of-genes-associated-with-reactive-gliosis-in-retinal-m%C3%A3-ller-cells
#12
Vijay P Sarthy, Hari Sawkar, V Joseph Dudley
PURPOSE/AIM OF THE STUDY: Photoreceptor degeneration is normally accompanied by reactive gliosis and gene expression changes in Müller (glial) cells. The signaling pathway involved inducing these changes in Müller cells is not known. It has been proposed that endothelin2 (EDN2) released by degenerating photoreceptors might induce gliotic changes in Müller cells. In the present study, we directly tested the hypothesis by determining whether treatment of Müller cell cultures with EDN2 results in upregulation of genes known to be expressed in activated Müller cells in vivo...
2015: Current Eye Research
https://www.readbyqxmd.com/read/25132557/combinatorial-targeting-of-early-pathways-profoundly-inhibits-neurodegeneration-in-a-mouse-model-of-glaucoma
#13
Gareth R Howell, Katharine H MacNicoll, Catherine E Braine, Ileana Soto, Danilo G Macalinao, Gregory L Sousa, Simon W M John
The endothelin system is implicated in various human and animal glaucomas. Targeting the endothelin system has great promise as a treatment for human glaucoma, but the cell types involved and the exact mechanisms of action are not clearly elucidated. Here, we report a detailed characterization of the endothelin system in specific cell types of the optic nerve head (ONH) during glaucoma in DBA/2J mice. First, we show that key components of the endothelin system are expressed in multiple cell types. We discover that endothelin 2 (EDN2) is expressed in astrocytes as well as microglia/monocytes in the ONH...
November 2014: Neurobiology of Disease
https://www.readbyqxmd.com/read/25118007/familial-co-segregation-of-coffin-lowry-syndrome-inherited-from-the-mother-and-autosomal-dominant-waardenburg-type-iv-syndrome-due-to-deletion-of-ednrb-inherited-from-the-father
#14
Jacob Loupe, Srirangan Sampath, Yves Lacassie
We report an African-American family that was identified after the proposita was referred for diagnostic evaluation at 4½ months with a history of Hirschsprung and dysmorphic features typical of Waardenburg syndrome (WS). Family evaluation revealed that the father had heterochromidia irides and hypertelorism supporting the clinical diagnosis of WS; however, examination of the mother revealed characteristic facial and digital features of Coffin-Lowry syndrome (CLS). Molecular testing of the mother identified a novel 2 bp deletion (c...
October 2014: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/24856564/blood-biomarkers-of-depression-track-clinical-changes-during-cognitive-behavioral-therapy
#15
Szabolcs Kéri, Csilla Szabó, Oguz Kelemen
BACKGROUND: Results from convergent genomics indicated new peripheral biomarkers for mood states. We sought to investigate the clinical utility of the BioM-10 Mood Panel, a peripheral biomarker set of low vs. high mood states, in the diagnosis of major depressive episode and to monitor the effectiveness of cognitive-behavioral therapy (CBT). METHOD: 44 patients with a first episode of major depression and 30 healthy control subjects participated in the study. The BioM-10 panel׳s gene expression profile was measured from whole peripheral blood with the Affymetrix Human Genome U133 Plus 2...
August 2014: Journal of Affective Disorders
https://www.readbyqxmd.com/read/24722437/direct-action-of-endothelin-1-on-podocytes-promotes-diabetic-glomerulosclerosis
#16
Olivia Lenoir, Marine Milon, Anne Virsolvy, Carole Hénique, Alain Schmitt, Jean-Marc Massé, Yuri Kotelevtsev, Masashi Yanagisawa, David J Webb, Sylvain Richard, Pierre-Louis Tharaux
The endothelin system has emerged as a novel target for the treatment of diabetic nephropathy. Endothelin-1 promotes mesangial cell proliferation and sclerosis. However, no direct pathogenic effect of endothelin-1 on podocytes has been shown in vivo and endothelin-1 signaling in podocytes has not been investigated. This study investigated endothelin effects in podocytes during experimental diabetic nephropathy. Stimulation of primary mouse podocytes with endothelin-1 elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs)...
May 2014: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/24651527/mapk-pathway-inhibition-enhances-the-efficacy-of-an-anti-endothelin-b-receptor-drug-conjugate-by-inducing-target-expression-in-melanoma
#17
Jyoti Asundi, Jennifer A Lacap, Suzanna Clark, Michelle Nannini, Leslie Roth, Paul Polakis
Therapies targeting the mitogen-activated protein (MAP) kinase pathway in melanoma have produced significant clinical responses; however, duration of response is limited by acquisition of drug resistance. Rational drug combinations may improve outcomes in this setting. We assessed the therapeutic combination of an antibody-drug conjugate (ADC) targeting the endothelin B receptor (EDNRB) with small-molecule inhibitors of the MAP kinase signaling pathway in melanoma. Cell lines and tumor models containing either mutant BRAF or NRAS, or wild-type for both, were exposed to small-molecule inhibitors of BRAF and MEK...
June 2014: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/24603425/vascular-tone-pathway-polymorphisms-in-relation-to-primary-open-angle-glaucoma
#18
J H Kang, S J Loomis, B L Yaspan, J C Bailey, R N Weinreb, R K Lee, P R Lichter, D L Budenz, Y Liu, T Realini, D Gaasterland, T Gaasterland, D S Friedman, C A McCarty, S E Moroi, L Olson, J S Schuman, K Singh, D Vollrath, G Wollstein, D J Zack, M Brilliant, A J Sit, W G Christen, J Fingert, J P Forman, E S Buys, P Kraft, K Zhang, R R Allingham, M A Pericak-Vance, J E Richards, M A Hauser, J L Haines, J L Wiggs, L R Pasquale
AIMS: Vascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG. METHODS: We used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes...
June 2014: Eye
https://www.readbyqxmd.com/read/24040226/a-novel-bidirectional-interaction-between-endothelin-3-and-retinoic-acid-in-rat-enteric-nervous-system-precursors
#19
Jonathan M Gisser, Ariella R Cohen, Han Yin, Cheryl E Gariepy
BACKGROUND: Signaling through the endothelin receptor B (EDNRB) is critical for the development of the enteric nervous system (ENS) and mutations in endothelin system genes cause Hirschsprung's aganglionosis in humans. Penetrance of the disease is modulated by other genetic factors. Mutations affecting retinoic acid (RA) signaling also produce aganglionosis in mice. Thus, we hypothesized that RA and endothelin signaling pathways may interact in controlling development of the ENS. METHODS: Rat immunoselected ENS precursor cells were cultured with the EDNRB ligand endothelin-3, an EDNRB-selective antagonist (BQ-788), and/or RA for 3 or 14 days...
2013: PloS One
https://www.readbyqxmd.com/read/23840513/genetic-analyses-of-a-three-generation-family-segregating-hirschsprung-disease-and-iris-heterochromia
#20
Long Cui, Emily Hoi-Man Wong, Guo Cheng, Manoel Firmato de Almeida, Man-Ting So, Pak-Chung Sham, Stacey S Cherny, Paul Kwong-Hang Tam, Maria-Mercè Garcia-Barceló
We present the genetic analyses conducted on a three-generation family (14 individuals) with three members affected with isolated-Hirschsprung disease (HSCR) and one with HSCR and heterochromia iridum (syndromic-HSCR), a phenotype reminiscent of Waardenburg-Shah syndrome (WS4). WS4 is characterized by pigmentary abnormalities of the skin, eyes and/or hair, sensorineural deafness and HSCR. None of the members had sensorineural deafness. The family was screened for copy number variations (CNVs) using Illumina-HumanOmni2...
2013: PloS One
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