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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/28815942/plasma-membrane-protein-profiling-in-beta-amyloid-treated-microglia-cell-line
#2
Virginia Correani, Laura Di Francesco, Giuseppina Mignogna, Cinzia Fabrizi, Stefano Leone, Alessandra Giorgi, Alessia Passeri, Roberto Casata, Lorenzo Fumagalli, Bruno Maras, M Eugenia Schininà
In the responsiveness of microglia to toxic stimuli, plasma membrane proteins play a key role. In this study we treated with a synthetic beta amyloid peptide murine microglial cells metabolically differently labelled with stable isotope amino acids (SILAC). The plasma membrane was selectively enriched by a multi-stage aqueous two-phase partition system. We were able to identify by 1D-LC-MS/MS analyses 1577 proteins, most of them are plasma membrane proteins according to the Gene Ontology annotation. An unchanged level of amyloid receptors in this data set, suggests that microglia preserve their responsiveness capability to the environment even after 24 h-challenge with amyloid peptides...
August 16, 2017: Proteomics
https://www.readbyqxmd.com/read/28814881/elevated-expression-of-neuropilin-2-associated-with-unfavorable-prognosis-in-hepatocellular-carcinoma
#3
Xiaogang Dong, Wenjia Guo, Shizhen Zhang, Tianchun Wu, Zhongquan Sun, Sheng Yan, Shusen Zheng
Neuropilin-2 (NRP2) is a single-pass transmembrane glycoprotein and has recently been detected in several human cancer cells. However, its clinical relevance in hepatocellular carcinoma (HCC) remains unclear. This study aimed at evaluating NRP2 expression and clinicopathological significance in HCC patients. Tissue microarray of 190 HCC patients from the First Affiliated Hospital of Zhejiang University was established, and immunohistochemical staining was performed for NRP2. The Kaplan-Meier analysis and Cox proportional hazard model were used to analyze the survival rate...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28810643/occludin-downregulation-in-high-glucose-is-regulated-by-sstr2-via-the-vegf-nrp1-akt-signaling-pathway-in-rf-6a-cells
#4
Mengling Li, Shuaiwei Wang, Songjiang Wang, Lei Zhang, Dongdong Wu, Ruisheng Yang, Ailing Ji, Yanzhang Li, Jun Wang
Occludin is a tight junction protein that forms the permeability barrier, which is typically disturbed in ischemic associated diseases. The aim of the present study was to determine whether somatostatin receptor 2 (SSTR2) in RF/6A cells is involved in the modulation of the downregulation of occludin induced by high glucose, and to evaluate the implicated molecules. RF/6A cells were maintained in Dulbecco's modified Eagle medium and treated with 0 or 30 mM D-glucose. SSTR2 agonist octreotide (OCT), OCT with SSTR2 antagonist cycle-somatostatin (c-SOM) and neuropilin 1 (NRP1) inhibitor ATWLPPR, respectively, were administered to RF/6A cells under high glucose conditions...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28806446/sema3a-reduces-sprouting-of-adult-rod-photoreceptors-in-vitro
#5
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/28804523/tri-methylation-of-h3k79-is-decreased-in-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-lung-cancer
#6
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/28796261/p53-r273h-upregulates-neuropilin-2-to-promote-cell-mobility-and-tumor-metastasis
#7
Tao Lv, Xianqiang Wu, Lijuan Sun, Qingyong Hu, Yang Wan, Liang Wang, Zhiqiang Zhao, Xiao Tu, Zhi-Xiong Jim Xiao
Mounting evidence indicates that hotspot p53 mutant proteins often possess gain-of-function property in promoting cell mobility and tumor metastasis. However, the molecular mechanisms are not totally understood. In this study, we demonstrate that the hotspot mutation, p53-R273H, promotes cell migration, invasion in vitro and tumor metastasis in vivo. p53-R273H significantly represses expression of DLX2, a homeobox protein involved in cell proliferation and pattern formation. We show that p53-R273H-mediated DLX2 repression leads to upregulation of Neuropilin-2 (NRP2), a multifunctional co-receptor involved in tumor initiation, growth, survival and metastasis...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28767395/prohibitin-relocated-to-the-front-ends-can-control-the-migration-directionality-of-colorectal-cancer-cells
#8
Li-Li Ma, Lan Shen, Gui-Hui Tong, Na Tang, Yang Luo, Li-Li Guo, Chun-Ting Hu, Ying-Xin Huang, Guan Huang, Fang-Yan Jing, Chao Liu, Zhuo-Yi Li, Na Zhou, Qian-Wen Yan, Yan Lei, Shi-Jie Zhu, Zhi-Qiang Cheng, Guang-Wen Cao, Yong-Jian Deng, Yan-Qing Ding
Directional migration is a cost-effective movement allowing invasion and metastatic spread of cancer cells. Although migration related to cytoskeletal assembly and microenvironmental chemotaxis has been elucidated, little is known about interaction between extracellular and intracellular molecules for controlling the migrational directionality. A polarized expression of prohibitin (PHB) in the front ends of CRC cells favors metastasis and is correlated with poor prognosis for 545 CRC patients. A high level of vascular endothelial growth factor (VEGF) in the interstitial tissue of CRC patients is associated with metastasis...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28738522/combination-of-nrp1-mediated-irgd-with-5-fluorouracil-suppresses-proliferation-migration-and-invasion-of-gastric-cancer-cells
#9
Li Zhang, Yanfeng Xing, Qi Gao, Xuejun Sun, Di Zhang, Gang Cao
Gastric cancer is one of the most of common cancers in the world. 5-Fluorouracil (5-FU) has been identified as one of the standard first-line chemotherapy drugs for locally advanced or metastatic gastric cancer. However, poor tumor penetration, bad selectivity and toxic side effects are the major limitations for the application of chemotherapy drugs in anticancer therapy. Recently, plenty of studies demonstrate that the novel tumor-homing peptide iRGD could promote the tumor-penetrating capability of chemotherapy drugs in multiple cancers, and neuropilin-1 (NRP1) protein is the critical mediator for iRGD...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28731029/nrp2-is-sufficient-to-instruct-circuit-formation-of-mitral-cells-to-mediate-odour-induced-attractive-social-responses
#10
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/28717010/phosphorylation-of-the-kainate-receptor-kar-auxiliary-subunit-neto2-at-serine-409-regulates-synaptic-targeting-of-the-kar-subunit-gluk1
#11
Richa Madan Lomash, Nengyin Sheng, Yan Li, Roger A Nicoll, Katherine W Roche
Synaptic strength at excitatory synapses is determined by the presence of glutamate receptors (i.e. AMPA, NMDA and kainate receptors) at the synapse. Synaptic strength is modulated by multiple factors including assembly of different receptor subunits, interaction with auxiliary subunits and post translational modifications of either the receptors or their auxiliary subunits. Using mass spectrometry, we find that the intracellular region of neuropilin and tolloid-like proteins (Neto)1 and Neto2, the auxiliary subunits of KARs are phosphorylated by multiple kinases in vitro...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28700345/platelet-derived-growth-factor-c-promotes-human-melanoma-aggressiveness-through-activation-of-neuropilin-1
#12
Federica Ruffini, Lauretta Levati, Grazia Graziani, Simona Caporali, Maria Grazia Atzori, Stefania D'Atri, Pedro M Lacal
Despite recent progress in advanced melanoma therapy, identification of signalling pathways involved in melanoma switch from proliferative to invasive states is still crucial to uncover new therapeutic targets for improving the outcome of metastatic disease. Neuropilin-1 (NRP-1), a co-receptor for vascular endothelial growth factor-A (VEGF-A) tyrosine kinase receptors (VEGFRs), has been suggested to play a relevant role in melanoma progression. NRP-1 can be activated by VEGF-A also in the absence of VEGFRs, triggering specific signal transduction pathways (e...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28695222/ratiometric-in-vivo-auditioning-of-targeted-silver-nanoparticles
#13
Kadri Toome, Anne-Mari A Willmore, Päärn Paiste, Allan Tobi, Kazuki N Sugahara, Kalle Kirsimäe, Erkki Ruoslahti, Gary B Braun, Tambet Teesalu
Attaching affinity ligands to nanoparticles (NPs) increases selectivity for targeting cells and tissues, and can result in improved sensitivity and reduced off-target toxicity in diagnostic and therapeutic systems. The decision over key features - NP size, shape, coating strategies and targeting ligands for clinical translation is often hampered by a lack of quantitative in vivo NP homing assays. Sensitive, internally controlled assays are needed which allow for quantitative comparisons (auditions) among various formulations of targeted NPs...
July 20, 2017: Nanoscale
https://www.readbyqxmd.com/read/28676569/vegf-a-and-neuropilin-1-nrp1-shape-axon-projections-in-the-developing-cns-via-dual-roles-in-neurons-and-blood-vessels
#14
Lynda Erskine, Urielle François, Laura Denti, Andy Joyce, Miguel Tillo, Freyja Bruce, Neil Vargesson, Christiana Ruhrberg
Visual information is relayed from the eye to the brain via retinal ganglion cell (RGC) axons. Mice lacking NRP1 or NRP1-binding VEGF-A isoforms have defective RGC axon organisation alongside brain vascular defects. It is not known whether axonal defects are caused exclusively by defective VEGF-A signalling in RGCs or are exacerbated by abnormal vascular morphology. Targeted NRP1 ablation in RGCs with a Brn3b(Cre) knock-in allele reduced axonal midline crossing at the optic chiasm and optic tract fasciculation...
July 1, 2017: Development
https://www.readbyqxmd.com/read/28667171/neuropilin-1-promotes-hedgehog-signaling-through-a-novel-cytoplasmic-motif
#15
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/28666257/neuropilin-1-is-a-glial-cell-line-derived-neurotrophic-factor-receptor-in-glioblastoma
#16
Shen Sun, Yu Lei, Qi Li, Yue Wu, Lin Zhang, Pei-Pei Mu, Guang-Quan Ji, Chuan-Xi Tang, Yu-Qian Wang, Jian Gao, Jin Gao, Li Li, Lang Zhuo, Yun-Qing Li, Dian-Shuai Gao
The aim of this study was to identify the receptor for glial cell line-derived neurotrophic factor (GDNF) in glioblastoma multiforme (GBM). After GST pull-down assays, membrane proteins purified from C6 rat glioma cells were subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS). The differentially expressed proteins were annotated using Gene Ontology, and neuropilin-1 (NRP1) was identified as the putative GDNF receptor in glioma. NRP1 was more highly expressed in human GBM brains and C6 rat glioma cells than in normal human brains or primary rat astrocytes...
June 27, 2017: Oncotarget
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
#17
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
https://www.readbyqxmd.com/read/28636974/sema3a-partially-reverses-vegf-effects-through-binding-to-neuropilin-1
#18
Bruna Palodetto, Adriana da Silva Santos Duarte, Matheus Rodrigues Lopes, Flavia Adolfo Corrocher, Fernanda Marconi Roversi, Fernanda Soares Niemann, Karla Priscila Vieira Ferro, Ana Leda Figueiredo Longhini, Paula Melo Campos, Patricia Favaro, Sara Teresinha Olalla Saad
Cross-talk between hematopoietic stem cells (HSCs) and bone marrow stromal cells (BMSCs) is essential for HSCs regulation and leukemogenesis. Studying bone marrow of myelodysplasia patients, a pre-leukemic condition, we found mRNA overexpression of vascular endothelial growth factor A (VEGFA) in CD34(+) HSCs and semaphorin 3A (SEMA3A) in BMSCs. To better understand the role of VEGFA and SEMA3A in leukemogenesis, we recruited 30 myelodysplastic syndrome (MDS) patients, 29 acute myeloid leukemia (6 secondary to MDS) patients and 12 controls...
June 3, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28627371/structure-activity-relationship-study-of-tetrapeptide-inhibitors-of-the-vascular-endothelial-growth-factor-a-binding-to-neuropilin-1
#19
Dagmara Tymecka, Piotr F J Lipiński, Bartłomiej Fedorczyk, Anna Puszko, Beata Wileńska, Gerard Y Perret, Aleksandra Misicka
Neuropilin-1 is considered as one of the key receptors responsible for signaling pathways involved in pathological angiogenesis necessary for tumor progression, therefore targeting of VEGF165 binding to NRP-1 could be a relevant strategy for antiangiogenic treatment. It was shown before that the VEGF165/NRP-1 interaction can be inhibited by short tetrapeptides with K/RXXR sequence. Here, we present a structure-activity relationship study of the systematic optimization of amino acid residues in positions 1-3 in the above tetrapeptides...
June 13, 2017: Peptides
https://www.readbyqxmd.com/read/28618167/neuropilin-1-regulated-by-mir-320-contributes-to-the-growth-and-metastasis-of-cholangiocarcinoma-cells
#20
Huaqiang Zhu, Xian Jiang, Xu Zhou, Xuesong Dong, Kai Xie, Chuncheng Yang, Hongchi Jiang, Xueying Sun, Jun Lu
BACKGROUND & AIMS: Neuropilin-1 (NRP-1) activates signalling pathways as multifunctional co-receptors in cancer cells. However, its role and how it is regulated by miRNAs in cholangiocarcinoma (CCA) have not yet been investigated. METHODS: The expression of NRP-1, miR-320 and key molecules involved in cell proliferation, migration and related signalling pathways were detected by immunohistochemistry, immunoblotting and qRT-PCR. Stable transfectants depleted of NRP-1 were generated...
June 15, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
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