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https://www.readbyqxmd.com/read/28817310/semaphorins-and-their-roles-in-airway-biology-potential-as-therapeutic-targets
#1
Hesam Movassagh, Forough Khadem, Abdelilah S Gounni
Semaphorins are a large family of proteins originally identified as axon guidance cues which play a crucial role in neural development. They are also ubiquitously expressed beyond the nervous system and contribute to regulation of essential cell functions such as cell migration, proliferation, and adhesion. Binding of semaphorins to their receptors, including plexins and neuropilins, triggers diverse signaling pathways which are involved in the pathogenesis of various diseases from cancer to autoimmune and allergic disorders...
August 17, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28792859/elucidating-the-role-of-plexin-d1-in-body-fat-distribution-and-susceptibility-to-metabolic-disease-using-a-zebrafish-model-system
#2
James E N Minchin, John F Rawls
Non-communicable diseases (NCDs) such as cardiovascular disease, diabetes and cancer were responsible for 68% of all deaths worldwide in 2012. The regional distribution of lipid deposited within adipose tissue (AT) - so called body fat distribution (BFD) - is a strong risk factor for NCDs. BFD is highly heritable; however, the genetic basis of BFD is almost entirely unknown. Genome-wide association studies have identified several loci associated with BFD, including at Plexin D1 (PLXND1) - a gene known to modulate angiogenesis...
July 27, 2017: Adipocyte
https://www.readbyqxmd.com/read/28765893/endothelial-semaphorin-7a-promotes-seawater-aspiration-induced-acute-lung-injury-through-plexin-c1-and-%C3%AE-1-integrin
#3
Minlong Zhang, Xue Yan, Wei Liu, Ruilin Sun, Yonghong Xie, Faguang Jin
Inflammation and edema are two main characteristics in seawater aspiration‑induced acute lung injury (ALI). In a previous study of the authors, it was demonstrated that endothelial semaphorin 7A (SEMA7A) serves an important role in the development of seawater‑induced inflammation and edema. However, the mechanism of endothelial SEMA7A‑mediated ALI remains unclear. Therefore, the authors explored the effect of SEMA7A in rat pulmonary microvascular endothelial cells (RPMVECs) and the interaction between endothelial SEMA7A and alveolar macrophages during seawater aspiration‑induced ALI...
July 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28765520/semaphorin-4c-plexin-b2-signaling-in-peripheral-sensory-neurons-is-pronociceptive-in-a-model-of-inflammatory-pain
#4
Eszter Paldy, Manuela Simonetti, Thomas Worzfeld, Kiran Kumar Bali, Lucas Vicuña, Stefan Offermanns, Rohini Kuner
Semaphorins and their transmembrane receptors, Plexins, are key regulators of axon guidance and development of neuronal connectivity. B-type Plexins respond to Class IV semaphorins and mediate a variety of developmental functions. Here we report that the expression of Plexin-B2 and its high-affinity ligand, Sema4C, persists in peripheral sensory neurons in adult life and is markedly increased in states of persistent pain in mice. Genetic deletion of Sema4C as well as adult-onset loss of Plexin-B2 leads to impairment of the development and duration of inflammatory hypersensitivity...
August 2, 2017: Nature Communications
https://www.readbyqxmd.com/read/28760660/semaphorin4d-drives-cd8-t-cell-lesional-trafficking-in-oral-lichen-planus-via-cxcl9-cxcl10-upregulations-in-oral-keratinocytes
#5
Yao Ke, Erle Dang, Shengxian Shen, Tongmei Zhang, Hongjiang Qiao, Yuqian Chang, Qing Liu, Gang Wang
Chemokine mediated CD8(+) T cell recruitment is an essential but not well-established event for the persistence of oral lichen planus (OLP). Semaphorin 4D (Sema4D)/CD100 is implicated in immune dysfunction, chemokine modulation and cell migration, which are critical aspects for OLP progression, but its implication in OLP pathogenesis has not been determined. In this study, we sought to explicate the effect of Sema4D on human oral keratinocytes and its capacity to drive CD8(+) T cell lesional trafficking via chemokine modulation...
July 28, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28739743/role-of-plexin-b1-in-a-breast-cancer-cohort-of-pakistani-patients-and-its-contribution-towards-cancer-metastasis-as-indicated-by-an-in-vitro-model
#6
Muhammad Faraz Arshad Malik, Syeda Kiran Riaz, S H Waqar, Farhan Haq, Lin Ye, Wen G Jiang
BACKGROUND/AIM: In the current study, the role of plexin B1 in breast cancer metastasis was explored. MATERIALS AND METHODS: Freshly-excised tumours along with background tissues of affected patients (n=121) were collected from Pakistani hospitals and processed for RNA isolation and cDNA synthesis. Using quantitative polymerase chain reaction, expression of plexin B1 was evaluated and correlated with clinicopathological parameters. Furthermore, involvement of plexin B1 in metastasis was explored by generating gene knockdown in MDA-MB-231 and MCF-7 breast cancer cells...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28689759/amplification-of-f-actin-disassembly-and-cellular-repulsion-by-growth-factor-signaling
#7
Jimok Yoon, Sang Bum Kim, Giasuddin Ahmed, Jerry W Shay, Jonathan R Terman
Extracellular cues that regulate cellular shape, motility, and navigation are generally classified as growth promoting (i.e., growth factors/chemoattractants and attractive guidance cues) or growth preventing (i.e., repellents and inhibitors). Yet, these designations are often based on complex assays and undefined signaling pathways and thus may misrepresent direct roles of specific cues. Here, we find that a recognized growth-promoting signaling pathway amplifies the F-actin disassembly and repulsive effects of a growth-preventing pathway...
July 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28665070/identification-of-downstream-genes-of-the-mtor-pathway-that-predict-recurrence-and-progression-in-non-muscle-invasive-high-grade-urothelial-carcinoma-of-the-bladder
#8
Subin Jin, In Ho Chang, Jin Wook Kim, Young Mi Whang, Ha Jeong Kim, Soon Auck Hong, Tae Jin Lee
Microarray analysis was used to investigate the lack of identified mammalian target of rapamycin (mTOR) pathway downstream genes to overcome cross-talk at non-muscle invasive high-grade (HG)-urothelial carcinoma (UC) of the bladder, gene expression patterns, gene ontology, and gene clustering by triple (p70S6K, S6K, and eIF4E) small interfering RNAs (siRNAs) or rapamycin in 5637 and T24 cell lines. We selected mTOR pathway downstream genes that were suppressed by siRNAs more than 2-fold, or were up-regulated or down-regulated by rapamycin more than 2-fold...
August 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28656251/identification-of-a-gene-expression-profile-associated-with-the-regulation-of-angiogenesis-in-endometrial-cancer
#9
Marcin Opławski, Mateusz Michalski, Andrzej Witek, Bogdan Michalski, Nikola Zmarzły, Agnieszka Jęda-Golonka, Maria Styblińska, Joanna Gola, Małgorzata Kasprzyk-Żyszczyńska, Urszula Mazurek, Andrzej Plewka
The publication of the human genome sequence provided direction in the search for novel diagnostic and therapeutic methods for the treatment of human diseases. The aim of the present study was to investigate the hypothesis that the expression profile of genes involved in the regulation of angiogenesis may be a marker in endometrial cancer that facilitates the diagnosis and prognosis of patients, as well as the identification of novel therapeutic targets. The current study included 36 patients with grade (G) 1 to 3 endometrial cancer, and a control group of patients consisting of females that qualified for the removal of the uterus...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28635959/optogenetic-activation-of-plexin-b1-reveals-contact-repulsion-between-osteoclasts-and-osteoblasts
#10
Abhijit Deb Roy, Taofei Yin, Shilpa Choudhary, Vladimir Rodionov, Carol C Pilbeam, Yi I Wu
During bone remodelling, osteoclasts induce chemotaxis of osteoblasts and yet maintain spatial segregation. We show that osteoclasts express the repulsive guidance factor Semaphorin 4D and induce contact inhibition of locomotion (CIL) in osteoblasts through its receptor Plexin-B1. To examine causality and elucidate how localized Plexin-B1 stimulation may spatiotemporally coordinate its downstream targets in guiding cell migration, we develop an optogenetic tool for Plexin-B1 designated optoPlexin. Precise optoPlexin activation at the leading edge of migrating osteoblasts readily induces local retraction and, unexpectedly, distal protrusions to steer cells away...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28632130/the-laminar-organization-of-the-drosophila-ellipsoid-body-is-semaphorin-dependent-and-prevents-the-formation-of-ectopic-synaptic-connections
#11
Xiaojun Xie, Masashi Tabuchi, Matthew P Brown, Sarah P Mitchell, Mark N Wu, Alex L Kolodkin
The ellipsoid body (EB) in the Drosophila brain is a central complex (CX) substructure that harbors circumferentially laminated ring (R) neuron axons and mediates multifaceted sensory integration and motor coordination functions. However, what regulates R axon lamination and how lamination affects R neuron function remain unknown. We show here that the EB is sequentially innervated by small-field and large-field neurons and that early developing EB neurons play an important regulatory role in EB laminae formation...
June 20, 2017: ELife
https://www.readbyqxmd.com/read/28624895/semaphorin4d-plexinb1-signaling-attenuates-photoreceptor-outer-segment-phagocytosis-by-reducing-rac1-activity-of-rpe-cells
#12
Ayelen Bulloj, Arvydas Maminishkis, Masayuki Mizui, Silvia C Finnemann
Semaphorins form a family of secreted and membrane-bound molecules that were identified originally as axonal guidance factors during neuronal development. Given their wide distribution in many including mature tissues, semaphorin 4D (sema4D) and its main functional receptor plexin B1 (plxnB1) are expected to fulfill additional functions that remain to be uncovered. A main characteristic of the plexin receptor family is its ability to reorganize the cytoskeleton. PlxnB1 specifically may directly interact with Rho family GTPases to regulate F-actin driven pathways in cells in culture...
June 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28558017/a-dual-strategy-expression-screen-for-candidate-connectivity-labels-in-the-developing-thalamus
#13
Olivia Bibollet-Bahena, Tatsuya Okafuji, Karsten Hokamp, Guy Tear, Kevin J Mitchell
The thalamus or "inner chamber" of the brain is divided into ~30 discrete nuclei, with highly specific patterns of afferent and efferent connectivity. To identify genes that may direct these patterns of connectivity, we used two strategies. First, we used a bioinformatics pipeline to survey the predicted proteomes of nematode, fruitfly, mouse and human for extracellular proteins containing any of a list of motifs found in known guidance or connectivity molecules. Second, we performed clustering analyses on the Allen Developing Mouse Brain Atlas data to identify genes encoding surface proteins expressed with temporal profiles similar to known guidance or connectivity molecules...
2017: PloS One
https://www.readbyqxmd.com/read/28536997/plxna3-variant-rs5945430-is-associated-with-severe-clinical-course-in-male-multiple-sclerosis-patients
#14
Moaz Qureshi, Mohamed Hatem, Raed Alroughani, Sindhu P Jacob, Rabeah Abbas Al-Temaimi
Multiple sclerosis (MS) exhibits sex bias in disease clinical course as male MS patients develop severe, progressive clinical course with accumulating disability. So far, no factors have been found associating with this sex bias in MS severity. We set out to determine the genetic factor contributing to MS male-specific progressive disease. This is an MS cross-sectional study involving 213 Kuwaiti MS patients recruited at Dasman Diabetes Institute. Exome sequencing was performed on 18 females and 8 male MS patients' genomic DNA...
May 23, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28512129/mammalian-o-mannosylation-of-cadherins-and-plexins-is-independent-of-protein-o-mannosyltransferases-1-and-2
#15
Ida Signe Bohse Larsen, Yoshiki Narimatsu, Hiren Jitendra Joshi, Zhang Yang, Oliver J Harrison, Julia Brasch, Lawrence Shapiro, Barry Honig, Sergey Y Vakhrushev, Henrik Clausen, Adnan Halim
Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix...
July 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28508207/new-aspects-of-the-seam4d-dependent-control-of-lymphocyte-activation
#16
E M Kuklina, I V Nekrasova
Novel targets for action of the class IV semaphorin Seam4D have been identified in the immune system. The low-affinity CD72 receptor for Seam4D was detected not only on B lymphocytes, but also in a proportion of T cells, whereas the high-affinity semaphorin receptor, plexin B1, originally considered to belong to non-immune cells, proved to be in a great proportion of intact T and B cells. Seam4D is constitutively expressed in B cells, which, along with T cells, can serve as a source of both membrane and soluble semaphorin...
March 2017: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/28467912/plexin-b2-and-semaphorin-4c-guide-t-cell-recruitment-and-function-in-the-germinal-center
#17
Hu Yan, Longyan Wu, Changming Shih, Shiyue Hou, Jingwen Shi, Tianyang Mao, Wenbin Chen, Bhavani Melvin, Robert J Rigby, Yingjia Chen, Haochen Jiang, Roland H Friedel, Carola G Vinuesa, Hai Qi
Follicular T helper (TFH) cells orchestrate the germinal center (GC) response locally. TFH localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here. we define an antigen-independent, contact-dependent, adhesive guidance system for TFH cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecule, which is highly expressed by GC B cells, and its transmembrane binding partner semaphorin 4C (Sema4C), which is upregulated on TFH cells...
May 2, 2017: Cell Reports
https://www.readbyqxmd.com/read/28440030/identification-of-target-genes-downstream-of-semaphorin6a-plexina2-signaling-in-zebrafish
#18
Sarah E Emerson, Riley M St Clair, Ashley L Waldron, Sierra R Bruno, Anna Duong, Heather E Driscoll, Bryan A Ballif, Sarah McFarlane, Alicia M Ebert
BACKGROUND: Semaphorin (Sema)/Plexin (Plxn) signaling is important for many aspects of neuronal development, however, the transcriptional regulation imposed by this signaling pathway is unknown. Previously, we identified an essential role for Sema6A/PlxnA2 signaling in regulating proliferation and cohesion of retinal precursor cells (RPCs) during early eye development. This study used RNA isolated from control, Sema6A-deficient and PlxnA2-deficient zebrafish embryos in a microarray analysis to identify genes that were differentially expressed when this signaling pathway was disrupted...
April 25, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28438183/semaphorin-plexin-signaling-influences-early-ventral-telencephalic-development-and-thalamocortical-axon-guidance
#19
Manuela D Mitsogiannis, Graham E Little, Kevin J Mitchell
BACKGROUND: Sensory processing relies on projections from the thalamus to the neocortex being established during development. Information from different sensory modalities reaching the thalamus is segregated into specialized nuclei, whose neurons then send inputs to cognate cortical areas through topographically defined axonal connections. Developing thalamocortical axons (TCAs) normally approach the cortex by extending through the subpallium; here, axonal navigation is aided by distributed guidance cues and discrete cell populations, such as the corridor neurons and the internal capsule (IC) guidepost cells...
April 24, 2017: Neural Development
https://www.readbyqxmd.com/read/28416516/semaphorin-4d-inhibits-neutrophil-activation-and-is-involved-in-the-pathogenesis-of-neutrophil-mediated-autoimmune-vasculitis
#20
Masayuki Nishide, Satoshi Nojima, Daisuke Ito, Hyota Takamatsu, Shohei Koyama, Sujin Kang, Tetsuya Kimura, Keiko Morimoto, Takashi Hosokawa, Yoshitomo Hayama, Yuhei Kinehara, Yasuhiro Kato, Takeshi Nakatani, Yoshimitsu Nakanishi, Takeshi Tsuda, Jeong Hoon Park, Toru Hirano, Yoshihito Shima, Masashi Narazaki, Eiichi Morii, Atsushi Kumanogoh
OBJECTIVES: Inappropriate activation of neutrophils plays a pathological role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The aim of this study was to investigate the functions of semaphorin 4D (SEMA4D) in regulation of neutrophil activation, and its involvement in AAV pathogenesis. METHODS: Serum levels of soluble SEMA4D were evaluated by ELISA. Blood cell-surface expression of membrane SEMA4D was evaluated by flow cytometry. To determine the functional interactions between neutrophil membrane SEMA4D and endothelial plexin B2, wild-type and SEMA4D(-/-) mice neutrophils were cultured with an endothelial cell line (MS1) stained with SYTOX green, and subjected to neutrophil extracellular trap (NET) formation assays...
April 17, 2017: Annals of the Rheumatic Diseases
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