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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/28806446/sema3a-reduces-sprouting-of-adult-rod-photoreceptors-in-vitro
#2
Frank Kung, Weiwei Wang, Tracy S Tran, Ellen Townes-Anderson
Purpose: Rod photoreceptor terminals respond to retinal injury with retraction and sprouting. Since the guidance cue Semaphorin3A (Sema3A) is observed in the retina after injury, we asked whether Sema3A contributes to structural plasticity in rod photoreceptors. Methods: We used Western blots and alkaline phosphatase (AP)-tagged neuropilin-1 (NPN-1) to detect the expression of Sema3A in an organotypic model of porcine retinal detachment. We then examined Sema3A binding to cultured salamander rod photoreceptors using AP-tagged Sema3A...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28805479/on-variants-and-disease-causing-mutations-case-studies-of-a-sema4a-variant-identified-in-inherited-blindness
#3
Laura Bryant, Olga Lozynska, Grace Han, Jessica I W Morgan, Xiaowu Gai, Albert M Maguire, Tomas Aleman, Jean Bennett
The p.R713Q variant of the semaphorin-4a-encoding gene, SEMA4a, has been reported to cause autosomal dominant retinitis pigmentosa. Here we show three families with retinal degeneration in which unaffected family members are either homozygous or heterozygous for the variant. The p.R713Q variant in SEMA4A is insufficient to cause either autosomal recessive or autosomal dominant retinitis pigmentosa and is unlikely to be pathogenic.
August 14, 2017: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28804523/tri-methylation-of-h3k79-is-decreased-in-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-lung-cancer
#4
Emilie Evanno, Julie Godet, Nathalie Piccirilli, Joëlle Guilhot, Serge Milin, Jean Marc Gombert, Benoit Fouchaq, Joëlle Roche
BACKGROUND: The epithelial-to-mesenchymal transition (EMT) enables epithelial cancer cells to acquire mesenchymal features and contributes to metastasis and resistance to treatment. This process involves epigenetic reprogramming for gene expression. We explored global histone modifications during TGF-β1-induced EMT in two non-small cell lung cancer (NSCLC) cell lines and tested different epigenetic treatment to modulate or partially reverse EMT. RESULTS: Loss of classical epithelial markers and gain of mesenchymal markers were verified in A549 and H358 cell lines during TGF-β1-induced EMT...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28793334/spheroid-growth-in-ovarian-cancer-alters-transcriptome-responses-for-stress-pathways-and-epigenetic-responses
#5
Trillitye Paullin, Chase Powell, Christopher Menzie, Robert Hill, Feng Cheng, Christopher J Martyniuk, Sandy D Westerheide
Ovarian cancer is the most lethal gynecological cancer, with over 200,000 women diagnosed each year and over half of those cases leading to death. These poor statistics are related to a lack of early symptoms and inadequate screening techniques. This results in the cancer going undetected until later stages when the tumor has metastasized through a process that requires the epithelial to mesenchymal transition (EMT). In lieu of traditional monolayer cell culture, EMT and cancer progression in general is best characterized through the use of 3D spheroid models...
2017: PloS One
https://www.readbyqxmd.com/read/28790351/whole-transcriptome-profiling-of-taste-bud-cells
#6
Sunil K Sukumaran, Brian C Lewandowski, Yumei Qin, Ramana Kotha, Alexander A Bachmanov, Robert F Margolskee
Analysis of single-cell RNA-Seq data can provide insights into the specific functions of individual cell types that compose complex tissues. Here, we examined gene expression in two distinct subpopulations of mouse taste cells: Tas1r3-expressing type II cells and physiologically identified type III cells. Our RNA-Seq libraries met high quality control standards and accurately captured differential expression of marker genes for type II (e.g. the Tas1r genes, Plcb2, Trpm5) and type III (e.g. Pkd2l1, Ncam, Snap25) taste cells...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28775366/microrna-143-and-145-modulate-the-phenotype-of-synovial-fibroblasts-in-rheumatoid-arthritis
#7
Bong-Ki Hong, Sungyong You, Seung-Ah Yoo, Dohyun Park, Daehee Hwang, Chul-Soo Cho, Wan-Uk Kim
Fibroblast-like synoviocytes (FLSs) constitute a major cell subset of rheumatoid arthritis (RA) synovia. Dysregulation of microRNAs (miRNAs) has been implicated in activation and proliferation of RA-FLSs. However, the functional association of various miRNAs with their targets that are characteristic of the RA-FLS phenotype has not been globally elucidated. In this study, we performed microarray analyses of miRNAs and mRNAs in RA-FLSs and osteoarthritis FLSs (OA-FLSs), simultaneously, to validate how dysregulated miRNAs may be associated with the RA-FLS phenotype...
August 4, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28765893/endothelial-semaphorin-7a-promotes-seawater-aspiration-induced-acute-lung-injury-through-plexin-c1-and-%C3%AE-1-integrin
#8
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
#9
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
#10
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/28754980/regulation-of-sema3c-and-the-interaction-between-cardiac-neural-crest-and-second-heart-field-during-outflow-tract-development
#11
Kazuki Kodo, Shinsuke Shibata, Sachiko Miyagawa-Tomita, Sang-Ging Ong, Hiroshi Takahashi, Tsutomu Kume, Hideyuki Okano, Rumiko Matsuoka, Hiroyuki Yamagishi
The cardiac neural crest cells (cNCCs) and the second heart field (SHF) play key roles in development of the cardiac outflow tract (OFT) for establishment of completely separated pulmonary and systemic circulations in vertebrates. A neurovascular guiding factor, Semaphorin 3c (Sema3c), is required for the development of the OFT, however, its regulation of the interaction between cNCCs and SHF remains to be determined. Here, we show that a Sema3c is a candidate that mediates interaction between cNCCs and the SHF during development of the OFT...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28736223/semaphorin-3a-in-ankylosing-spondylitis
#12
Hsien-Tzung Liao, Yuh-Feng Lin, Chung-Tei Chou, Chang-Youh Tsai
BACKGROUND/PURPOSE: To determine serum semaphorin 3A (Sema 3A) levels in ankylosing spondylitis (AS). METHODS: Serum Sema 3A was measured in 46 AS patients and 30 healthy controls (HCs). For the patients, we recorded demographic data, disease activity, functional index & global assessment, detected human leukocyte antigen-B27 (HLA-B27), and measured erythrocyte sedimentation rate (ESR) & C-reactive protein (CRP). RESULTS: Sema 3A was higher in AS patients than in HCs (3...
July 14, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28731029/nrp2-is-sufficient-to-instruct-circuit-formation-of-mitral-cells-to-mediate-odour-induced-attractive-social-responses
#13
Kasumi Inokuchi, Fumiaki Imamura, Haruki Takeuchi, Ryang Kim, Hiroyuki Okuno, Hirofumi Nishizumi, Haruhiko Bito, Takefumi Kikusui, Hitoshi Sakano
Odour information induces various innate responses that are critical to the survival of the individual and for the species. An axon guidance molecule, Neuropilin 2 (Nrp2), is known to mediate targeting of olfactory sensory neurons (primary neurons), to the posteroventral main olfactory bulb (PV MOB) in mice. Here we report that Nrp2-positive (Nrp2(+)) mitral cells (MCs, second-order neurons) play crucial roles in transmitting attractive social signals from the PV MOB to the anterior part of medial amygdala (MeA)...
July 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28729362/sema3f-semaphorin-3f-selectively-drives-an-extraembryonic-proangiogenic-program
#14
Donatella Regano, Alessia Visintin, Fabiana Clapero, Federico Bussolino, Donatella Valdembri, Federica Maione, Guido Serini, Enrico Giraudo
OBJECTIVE: Molecular pathways governing blood vessel patterning are vital to vertebrate development. Because of their ability to counteract proangiogenic factors, antiangiogenic secreted Sema3 (class 3 semaphorins) control embryonic vascular morphogenesis. However, if and how Sema3 may play a role in the control of extraembryonic vascular development is presently unknown. APPROACH AND RESULTS: By characterizing genetically modified mice, here, we show that surprisingly Sema3F acts instead as a selective extraembryonic but not intraembryonic proangiogenic cue...
July 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28698137/ssecks-akap12-induces-repulsion-between-human-prostate-cancer-and-microvessel-endothelial-cells-through-the-activation-of-semaphorin-3f
#15
Wen Xie, Wei Su, Lijuan Zhang, Qingkun Shang, Bing Su
Metastasis remains the primary cause of prostate cancer related death. Cancer cells need to contact endothelial cells and disrupt endothelial junctions to cross the endothelium for invasion and metastasis. The suppression of heterotypic repulsion between cancer and endothelial cells allows cancer cells to invade into the surrounding tissue. Here, we demonstrate that SSeCKS/AKAP12 induced repulsion between human prostate cancer and microvessel endothelial cells, which was mediated by an angiogenesis inhibitor Semaphorin 3F...
September 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28692932/axon-guidance-pathways-served-as-common-targets-for-human-speech-language-evolution-and-related-disorders
#16
Huimeng Lei, Zhangming Yan, Xiaohong Sun, Yue Zhang, Jianhong Wang, Caihong Ma, Qunyuan Xu, Rui Wang, Erich D Jarvis, Zhirong Sun
Human and several nonhuman species share the rare ability of modifying acoustic and/or syntactic features of sounds produced, i.e. vocal learning, which is the important neurobiological and behavioral substrate of human speech/language. This convergent trait was suggested to be associated with significant genomic convergence and best manifested at the ROBO-SLIT axon guidance pathway. Here we verified the significance of such genomic convergence and assessed its functional relevance to human speech/language using human genetic variation data...
July 7, 2017: Brain and Language
https://www.readbyqxmd.com/read/28689759/amplification-of-f-actin-disassembly-and-cellular-repulsion-by-growth-factor-signaling
#17
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/28683823/sema3a-drastically-suppresses-tumor-growth-in-oral-cancer-xenograft-model-of-mice
#18
Chao Huang, Yi Wang, Jian-Hua Huang, Weixian Liu
BACKGROUND: Multiple studies suggest anti-angiogenesis to be a promising and rational option in cancer treatment. Interestingly, the axonal sprouting inhibitor semaphorin 3A (Sema3A), a potent suppressor of tumor angiogenesis in various cancer models, is lowly expressed in human oral cancer. Thus, we hypothesized that overexpression of Sema3A in human oral cancer cells may have potential therapeutic effects. METHODS: The LentiSema3A-EGFP was first constructed and transduced to the tongue squamous cell carcinoma cell line SSC-9...
July 6, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28667171/neuropilin-1-promotes-hedgehog-signaling-through-a-novel-cytoplasmic-motif
#19
Justine M Pinskey, Nicole E Franks, Alexandra N McMellen, Roman J Giger, Benjamin L Allen
Hedgehog (HH) signaling critically regulates embryonic and postnatal development as well as adult tissue homeostasis, and its perturbation can lead to developmental disorders, birth defects, and cancers. Neuropilins (NRPs), which have well-defined roles in Semaphorin and VEGF signaling, positively regulate HH pathway function, although their mechanism of action in HH signaling remains unclear. Here, using luciferase-based reporter assays, we provide evidence that NRP1 regulates HH signaling, specifically at the level of GLI transcriptional activator function...
June 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28659345/ablation-of-neuropilin-1-in-myeloid-cells-exacerbates-high-fat-diet-induced-insulin-resistance-through-nlrp3-inflammasome-in-vivo
#20
Xiaoyan Dai, Imoh Okon, Zhaoyu Liu, Tatiana Bedarida, Qilong Wang, Tharmarajan Ramprasath, Miao Zhang, Ping Song, Ming-Hui Zou
Neuropilin 1 (Nrp1), a co-receptor for class 3 semaphorins and growth factors, is highly expressed in vascular cells and myeloid cells including macrophages. Unlike well characterized pro-angiogeneic functions of endothelial cell Nrp1, the contributions of macrophage Nrp1 within the context of metabolic dysfunction remain to be established. The aim of this study was to determine the contributions of macrophage Nrp1 in high-fat diet (HFD; 60% kcal, 16 weeks)-instigated insulin resistance in vivo Insulin sensitivity and Nlrp3 inflammasome activation were monitored in HFD-fed wild-type (WT) and myeloid cell-specific Nrp1 knockout (Nrp1(myel-KO)) mice...
June 28, 2017: Diabetes
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