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https://www.readbyqxmd.com/read/27913633/chemorepellent-semaphorin-3e-negatively-regulates-neutrophil-migration-in-vitro-and-in-vivo
#1
Hesam Movassagh, Abeer Saati, Saravanan Nandagopal, Ashfaque Mohammed, Nazanin Tatari, Lianyu Shan, Jonathan S Duke-Cohan, Keith R Fowke, Francis Lin, Abdelilah S Gounni
Neutrophil migration is an essential step in leukocyte trafficking during inflammatory responses. Semaphorins, originally discovered as axon guidance cues in neural development, have been shown to regulate cell migration beyond the nervous system. However, the potential contribution of semaphorins in the regulation of neutrophil migration is not well understood. This study examines the possible role of a secreted chemorepellent, Semaphorin 3E (Sema3E), in neutrophil migration. In this study, we demonstrated that human neutrophils constitutively express Sema3E high-affinity receptor, PlexinD1...
December 2, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27912840/the-semaphorins-and-their-receptors-as-modulators-of-tumor-progression
#2
Gera Neufeld, Yelena Mumblat, Tanya Smolkin, Shira Toledano, Inbal Nir-Zvi, Keren Ziv, Ofra Kessler
The semaphorins were initially characterized as repulsive axon guidance factors. However, they are currently also recognized as important regulators of diverse biological processes which include regulation of immune responses, angiogenesis, organogenesis, and a variety of additional physiological and developmental functions. The semaphorin family consists of more than 20 genes divided into seven subfamilies, all of which contain the sema domain signature. They usually transduce signals by activation of receptors belonging to the plexin family, either directly, or indirectly following the binding of some semaphorins to receptors of the neuropilin family which subsequently associate with plexins...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27911862/overexpression-of-semaphorin-3e-enhances-pancreatic-cancer-cell-growth-and-associates-with-poor-patient-survival
#3
Lin-Kin Yong, Syeling Lai, Zhengdong Liang, Ethan Poteet, Fengju Chen, George van Buren, William Fisher, Qianxing Mo, Changyi Chen, Qizhi Yao
Semaphorin-3E (Sema3E) is a member of an axon guidance gene family, and has recently been reported to contribute to tumor progression and metastasis. However, its role in pancreatic cancer is yet unknown and uncharacterized. In this study, we showed that Sema3E is overexpressed in human pancreatic cancer, and that high Sema3E levels are associated with tumor progression and poor survival. Interestingly, we also observed Sema3E expression in the nucleus, even though Sema3E is reported to be a secreted protein...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27906605/current-drug-design-to-target-the-semaphorin-neuropilin-plexin-complexes
#4
Lionel A T Meyer, Justine Fritz, Marie Pierdant-Mancera, Dominique Bagnard
The Semaphorin/Neuropilin/Plexin (SNP) complexes control a wide range of biological processes. Consistently, activity deregulation of these complexes is associated with many diseases. The increasing knowledge on SNP had in turn validated these molecular complexes as novel therapeutic targets. Targeting SNP activities by small molecules, antibodies and peptides or by soluble Semaphorins have been proposed as new therapeutic approach. This review is focusing on the latest demonstration of this potential and discusses some of the key questions that need to be addressed before translating SNP targeting into clinically relevant approaches...
December 1, 2016: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/27898465/the-intragraft-microenvironment-as-a-central-determinant-of-chronic-rejection-or-local-immunoregulation-tolerance
#5
Johannes Wedel, Hironao Nakayama, Nora M Kochupurakkal, Josephine Koch, Michael Klagsbrun, Diane R Bielenberg, David M Briscoe
PURPOSE OF REVIEW: Chronic rejection is associated with persistent mononuclear cell recruitment, endothelial activation and proliferation, local tissue hypoxia and related biology that enhance effector immune responses. In contrast, the tumor microenvironment elicits signals/factors that inhibit effector T cell responses and rather promote immunoregulation locally within the tissue itself. The identification of immunoregulatory check points and/or secreted factors that are deficient within allografts is of great importance in the understanding and prevention of chronic rejection...
November 24, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27897208/beta-1-integrin-ligation-and-tlr-ligation-enhance-gm-csf-induced-aldh1a2-expression-in-dendritic-cells-but-differentially-regulate-their-anti-inflammatory-properties
#6
Aya Yokota-Nakatsuma, Yoshiharu Ohoka, Hajime Takeuchi, Si-Young Song, Makoto Iwata
Retinoic acid (RA)-producing CD103(+) mature dendritic cells (DCs) in mesenteric lymph nodes (MLNs) play crucial roles in gut immunity. GM-CSF and RA contribute to the expression of the RA-producing enzyme ALDH1A2. However, additional signals appeared to be required for inducing ALDH1A2(high) mature DCs from immature DCs. We found here that TLR ligands (Ls) and immobilized E-cadherin could provide such signals in FLT3-L-generated bone marrow (BM)-derived DCs after treatment with GM-CSF and the RA receptor agonist Am80...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895757/expression-of-semaphorin-6d-and-its-receptor-plexin-a1-in-gastric-cancer-and-their-association-with-tumor-angiogenesis
#7
Yanjie Lu, Qian Xu, Lei Chen, Yanzhen Zuo, Shaochen Liu, Yatao Hu, Xiaoru Li, Yuhong Li, Xiangyang Zhao
The semaphorin and plexin family of ligands and receptor proteins provides important axon growth and guidance cues required for development. In recent years, studies have expanded their role in the regulation of cardiac morphogenesis and tumorigenesis. However, the mechanism responsible for their role in regulating cancer development and progression has not been clarified. In the present study, semaphorin 6D (Sema6D) and its receptor plexin-A1 were identified to be expressed at high levels in vascular epithelial cells within gastric cancer, and were positively correlated with vascular endothelial growth factor receptor 2 (VEGFR2)...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27890825/the-expression-of-chemorepulsive-guidance-receptors-and-the-regenerative-abilities-of-spinal-projecting-neurons-after-spinal-cord-injury
#8
Jie Chen, Cindy Laramore, Michael I Shifman
Spinal cord injury (SCI) in mammals leads to permanent loss of function because axons do not regenerate in the central nervous system (CNS). To date, treatments based on neutralizing inhibitory environmental cues, such as the myelin-associated growth inhibitors and chondroitin sulfate proteoglycans, or on adding neurotrophic factors, have had limited success in enhancing regeneration. Published studies suggested that multiple axon guidance cues (repulsive guidance molecule (RGM) family, semaphorins, ephrins, and netrins) persist in adult animals, and that their expression is upregulated after CNS injury...
November 24, 2016: Neuroscience
https://www.readbyqxmd.com/read/27881703/semaphorin-4c-protects-against-allergic-inflammation-requirement-of-regulatory-cd138-plasma-cells
#9
Di Xue, Gabriel N Kaufman, Marieme Dembele, Marianne Beland, Amir H Massoud, Barbara C Mindt, Ryan Fiter, Elizabeth D Fixman, James G Martin, Roland H Friedel, Maziar Divangahi, Jörg H Fritz, Bruce D Mazer
The regulatory properties of B cells have been studied in autoimmune diseases; however, their role in allergic diseases is poorly understood. We demonstrate that Semaphorin 4C (Sema4C), an axonal guidance molecule, plays a crucial role in B cell regulatory function. Mice deficient in Sema4C exhibited increased airway inflammation after allergen exposure, with massive eosinophilic lung infiltrates and increased Th2 cytokines. This phenotype was reproduced by mixed bone marrow chimeric mice with Sema4C deficient only in B cells, indicating that B lymphocytes were the key cells affected by the absence of Sema4C expression in allergic inflammation...
November 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27880905/semaphorin-3g-provides-a-repulsive-guidance-cue-to-lymphatic-endothelial-cells-via-neuropilin-2-plexind1
#10
Xinyi Liu, Akiyoshi Uemura, Yoko Fukushima, Yutaka Yoshida, Masanori Hirashima
The vertebrate circulatory system is composed of closely related blood and lymphatic vessels. It has been shown that lymphatic vascular patterning is regulated by blood vessels during development, but its molecular mechanisms have not been fully elucidated. Here, we show that the artery-derived ligand semaphorin 3G (Sema3G) and the endothelial cell receptor PlexinD1 play a role in lymphatic vascular patterning. In mouse embryonic back skin, genetic inactivation of Sema3G or PlexinD1 results in abnormal artery-lymph alignment and reduced lymphatic vascular branching...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27858721/axon-guidance-molecule-expression-after-cell-therapy-in-a-mouse-model-of-parkinson-s-disease
#11
Joanna Kalaani, Rochea Joëlle, Eva Hamade, Bassam Badran, Mohamed Jaber, Afsaneh Gaillard, Laetitia Prestoz
BACKGROUND: Cell therapy is a promising approach for Parkinson's disease (PD). Others and we have previously shown that transplantation of ventral mesencephalic fetal cells into substantia nigra (SN) in an animal model of PD enables anatomical and functional repair of the degenerated pathway. However, the molecular basis of this repair is still largely unknown. OBJECTIVE: In this work, we studied the expression of several axon guidance molecules that may be implicated in the repair of the degenerated nigrostriatal pathway...
November 16, 2016: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/27858201/semaphorin3a-neuropilin1-signalling-is-involved-in-the-generation-of-cortical-interneurons
#12
William D Andrews, Melissa Barber, Marion Nemitz, Fani Memi, John G Parnavelas
Cortical interneurons are generated predominantly in the medial ganglionic eminence of the ventral telencephalon and migrate to the cortex during embryonic development. These cells express neuropilin (Nrp1 and Nrp2) receptors which mediate their response to the chemorepulsive class 3 semaphorin (Sema) ligands. We show here that semaphorins Sema3A and Sema3F are expressed in layers adjacent to cortical interneuron migratory streams as well as in the striatum, suggesting they may have a role in guiding these cells throughout their journey...
November 17, 2016: Brain Structure & Function
https://www.readbyqxmd.com/read/27856318/sympathetic-nerve-repulsion-inhibited-by-designer-molecules-in-vitro-and-role-in-experimental-arthritis
#13
Julia Kunath, Nicolas Delaroque, Michael Szardenings, Ines Neundorf, Rainer H Straub
AIMS: In rheumatoid arthritis and collagen type II arthritis (CIA), sympathetic nerve fibers get lost in inflamed tissue. The process is probably induced by nerve repellent factors like semaphorin 3F (SEMA3F). Repulsion of sympathetic nerve fibers in inflamed tissue has proinflammatory effects due to the loss of anti-inflammatory neurotransmitters. We hypothesized that design molecules like antibodies and specific peptides that inhibit nerve fiber repulsion can ameliorate CIA. MATERIALS AND METHODS: Two blocking antibodies were used and four blocking peptides were generated using the phage display technique with the targets of SEMA3F and plexin-A2...
November 14, 2016: Life Sciences
https://www.readbyqxmd.com/read/27825676/expression-of-hypoxia-induced-semaphorin-7a-correlates-with-the-severity-of-inflammation-and-osteoclastogenesis-in-experimentally-induced-periapical-lesions
#14
Miao He, Zhuan Bian
OBJECTIVE: While hypoxia and inflammation are intimately linked, the effects of inflammatory hypoxia on the pathogenesis of periapical lesions remain largely unknown. The aim of this study was to examine hypoxia during the progression of experimentally induced rat periapical lesions, and to derive correlations between hypoxia-induced Semaphorin 7A (Sema7a) expression, severity of inflammation, and osteoclastogenesis in the lesions. DESIGN: Periapical lesions were developed after mandibular first molar pulp exposure in forty Sprague-Dawley rats...
October 29, 2016: Archives of Oral Biology
https://www.readbyqxmd.com/read/27822415/downregulation-of-semaphorin-3f-is-associated-with-poor-prognostic-significance-in-osteosarcoma-patients
#15
Ming-Han Liu, Wen-Juan Fu, You-Hong Cui, Qiao-Nan Guo, Yue Zhou
The secreted axonal guidance molecular, Semaphorin-3F (SEMA3F), is widely expressed outside the central nervous system and inhibits tumor growth and metastasis. However, the role of SEMA3F expression in the osteosarcoma prognosis has not been elaborated. This study aimed to evaluate SEMA3F expression level in osteosarcoma and assess its prognostic value for patients. SEMA3F protein expression was detected by immunohistochemistry (IHC) in 112 cases of osteosarcoma. Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the prognostic significance of SEMA3F...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27820602/an-interferon-%C3%AE-resistant-and-nlrp3-inflammasome-independent-subtype-of-eae-with-neuronal-damage
#16
Makoto Inoue, Po-Han Chen, Stephen Siecinski, Qi-Jing Li, Chunlei Liu, Lawrence Steinman, Simon G Gregory, Eric Benner, Mari L Shinohara
Inflammation induced by innate immunity influences the development of T cell-mediated autoimmunity in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). We found that strong activation of innate immunity induced Nod-like receptor protein 3 (NLRP3) inflammasome-independent and interferon-β (IFNβ)-resistant EAE (termed type B EAE), whereas EAE induced by weak activation of innate immunity requires the NLRP3 inflammasome and is sensitive to IFNβ treatment. Instead, an alternative inflammatory mechanism, including membrane-bound lymphotoxin-β receptor (LTβR) and CXC chemokine receptor 2 (CXCR2), is involved in type B EAE development, and type B EAE is ameliorated by antagonizing these receptors...
November 7, 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27817751/novel-insight-into-triple-negative-breast-cancers-the-emerging-role-of-angiogenesis-and-antiangiogenic-therapy
#17
Cornelia Braicu, Roxana Chiorean, Alexandru Irimie, Sergiu Chira, Ciprian Tomuleasa, Emilian Neagoe, Angelo Paradiso, Patriciu Achimas-Cadariu, Vladimir Lazar, Ioana Berindan-Neagoe
Triple-negative breast cancer (TNBC) is a heterogeneous group of tumours characterised by lack of expression of oestrogen-, progesterone- and human epidermal growth factor receptors. TNBC, which represents approximately 15% of all mammary tumours, has a poor prognosis because of an aggressive behaviour and the lack of specific treatment. Accordingly, TNBC has become a major focus of research into breast cancer and is now classified into several molecular subtypes, each with a different prognosis. Pathological angiogenesis occurs at a late stage in the proliferation of TNBC and is associated with invasion and metastasis; there is an association with metabolic syndrome...
November 7, 2016: Expert Reviews in Molecular Medicine
https://www.readbyqxmd.com/read/27803667/wedelolactone-enhances-osteoblastogenesis-but-inhibits-osteoclastogenesis-through-sema3a-nrp1-plexina1-pathway
#18
Yan-Qiu Liu, Xiao-Fei Han, Jun-Xia Bo, Hui-Peng Ma
Bone remodeling balance is maintained by tight coupling of osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Thus, agents with the capacity to regulate osteoblastogenesis and osteoclastogenesis have been investigated for therapy of bone-related diseases such as osteoporosis. In this study, we found that wedelolactone, a compound isolated from Ecliptae herba, and a 9-day incubation fraction of conditioned media obtained from wedelolactone-treated bone marrow mesenchymal stem cell (BMSC) significantly inhibited tartrate-resistant acid phosphatase (TRAP) activity in RANKL-stimulated osteoclastic RAW264...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27799363/sema3d-controls-collective-endothelial-cell-migration-by-distinct-mechanisms-via-nrp1-and-plxnd1
#19
Mailin Julia Hamm, Bettina Carmen Kirchmaier, Wiebke Herzog
During cardiovascular development, tight spatiotemporal regulation of molecular cues is essential for controlling endothelial cell (EC) migration. Secreted class III Semaphorins play an important role in guidance of neuronal cell migration and were lately linked to regulating cardiovascular development. Recently, SEMA3D gene disruptions were associated with cardiovascular defects in patients; however, the mechanisms of action were not revealed. Here we show for the first time that Sema3d regulates collective EC migration in zebrafish through two separate mechanisms...
November 7, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27798666/a-novel-physiological-glycosaminoglycan-deficient-splice-variant-of-neuropilin-1-is-anti-tumorigenic-in-vitro-and-in-vivo
#20
Céline Hendricks, Johanne Dubail, Laura Brohée, Yves Delforge, Alain Colige, Christophe Deroanne
Neuropilin-1 (NRP1) is a transmembrane protein acting as a co-receptor for several growth factors and interacting with other proteins such as integrins and plexins/semaphorins. It is involved in axonal development, angiogenesis and cancer progression. Its primary mRNA is subjected to alternative splicing mechanisms generating different isoforms, some of which lack the transmembrane domain and display antagonist properties to NRP1 full size (FS). NRP1 is further post-translationally modified by the addition of glycosaminoglycans (GAG) side chains through an O-glycosylation site at serine612...
2016: PloS One
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