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https://www.readbyqxmd.com/read/29671604/neuropilin-2-regulates-airway-inflammatory-responses-to-inhaled-lipopolysaccharide
#1
Robert M Immormino, David C Lauzier, Hideki Nakano, Michelle L Hernandez, Neil E Alexis, Andrew L Ghio, Stephen L Tilley, Claire M Doerschuk, David B Peden, Donald N Cook, Timothy P Moran
Neuropilins are multifunctional receptors that play important roles in immune regulation. Neuropilin-2 (NRP2) is expressed in the lungs, but whether it regulates airway immune responses is unknown. Here, we report that Nrp2 is weakly expressed by alveolar macrophages (AM) in the steady-state, but is dramatically up-regulated following in vivo lipopolysaccharide (LPS) inhalation. Ex vivo treatment of human AM with LPS also increased NRP2 mRNA expression and cell-surface display of NRP2 protein. LPS-induced Nrp2 expression in AM was dependent upon the MyD88 signaling pathway and the transcription factor nuclear factor kappa B (NFκB)...
April 19, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29671086/the-nrp1-migraine-risk-variant-shows-evidence-of-association-with-menstrual-migraine
#2
Charmaine E Pollock, Heidi G Sutherland, Bridget H Maher, Rodney A Lea, Larisa M Haupt, Alison Frith, E Anne MacGregor, Lyn R Griffiths
BACKGROUND: In 2016, a large meta-analysis brought the number of susceptibility loci for migraine to 38. While sub-type analysis for migraine without aura (MO) and migraine with aura (MA) found some loci showed specificity to MO, the study did not test the loci with respect to other subtypes of migraine. This study aimed to test the hypothesis that single nucleotide polymorphisms (SNPs) robustly associated with migraine are individually or collectively associated with menstrual migraine (MM)...
April 18, 2018: Journal of Headache and Pain
https://www.readbyqxmd.com/read/29661844/plexin-a4-plexin-d1-complexes-convey-semaphorin-3c-signals-to-induce-cytoskeletal-collapse-in-the-absence-of-neuropilins
#3
Tatyana Smolkin, Inbal Nir-Zvi, Nerri Duvshani, Yelena Mumblat, Ofra Kessler, Gera Neufeld
Class-3 semaphorin guidance factors bind to receptor complexes containing neuropilin and plexin receptors. A semaphorin may bind to several receptor complexes containing somewhat different constituents, resulting in diverse effects on cell migration. U87MG glioblastoma cells express both neuropilins and the four class-A plexins. They respond by cytoskeletal collapse and cell contraction to sema3A or sema3B but fail to contract in response to Sema3C, Sema3D, Sema3G or sema3E even when class-A plexins are over-expressed in the cells...
April 16, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29659486/vascular-endothelial-growth-factor-a-exerts-diverse-cellular-effects-via-small-g-proteins-rho-and-rap
#4
REVIEW
Akio Shimizu, Dimitar P Zankov, Misuzu Kurokawa-Seo, Hisakazu Ogita
Vascular endothelial growth factors (VEGFs) include five molecules (VEGF-A, -B, -C, -D, and placental growth factor), and have various roles that crucially regulate cellular functions in many kinds of cells and tissues. Intracellular signal transduction induced by VEGFs has been extensively studied and is usually initiated by their binding to two classes of transmembrane receptors: receptor tyrosine kinase VEGF receptors (VEGF receptor-1, -2 and -3) and neuropilins (NRP1 and NRP2). In addition to many established results reported by other research groups, we have previously identified small G proteins, especially Ras homologue gene (Rho) and Ras-related protein (Rap), as important mediators of VEGF-A-stimulated signaling in cancer cells as well as endothelial cells...
April 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29648813/small-molecule-neuropilin-1-antagonists-combine-anti-angiogenic-and-anti-tumour-activity-with-immune-modulation-through-reduction-of-transforming-growth-factor-beta-tgf%C3%AE-production-in-regulatory-t-cells
#5
Jonathan Powell, Filipa Mota, David Steadman, Christelle Soudy, Jeremy T Miyauchi, Stuart Crosby, Ashley Jarvis, Tifelle Reisinge, Natalie Winfield, Graham Evans, Aled Finniear, Tamas Yelland, Yi-Tai Chou, A W Edith Chan, Andrew O'Leary, Lili Cheng, Dan Liu, Ntina Fotinou, Carla Milagre, John F Martin, Haiyan Jia, Paul Frankel, Snezana Djordjevic, Stella E Tsirka, Ian C Zachary, David L Selwood
We report the design, synthesis and comprehensive studybiological evaluation of a range ofsome potent small-molecule neuropilin-1 (NRP1) antagonists. NRP1 is implicated in the immune response to tumours, particularly in Treg cell fragility, required for PD1 checkpoint blockade. The design of these compounds was based on a previously identified compound EG00229, EG00229 which was used a starting point for optimisation. Through targeting of specific amino-acid residues additional H-bonding interactions were introduced, which led to increases in binding affinity and potency...
April 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29642487/semaphorin-3c-and-its-receptors-in-cancer-and-cancer-stem-like-cells
#6
REVIEW
Jing Hao, Jennifer S Yu
Neurodevelopmental programs are frequently dysregulated in cancer. Semaphorins are a large family of guidance cues that direct neuronal network formation and are also implicated in cancer. Semaphorins have two kinds of receptors, neuropilins and plexins. Besides their role in development, semaphorin signaling may promote or suppress tumors depending on their context. Sema3C is a secreted semaphorin that plays an important role in the maintenance of cancer stem-like cells, promotes migration and invasion, and may facilitate angiogenesis...
April 8, 2018: Biomedicines
https://www.readbyqxmd.com/read/29629840/proteomics-detection-of-s100a6-in-tumor-tissue-interstitial-fluid-and-evaluation-of-its-potential-as-a-biomarker-of-cholangiocarcinoma
#7
Sudarat Onsurathum, Ornuma Haonon, Porntip Pinlaor, Chawalit Pairojkul, Narong Khuntikeo, Raynoo Thanan, Sittiruk Roytrakul, Somchai Pinlaor
Tumor interstitial fluid contains tumor-specific proteins that may be useful biomarkers for cancers. In this study, we identified proteins present in cholangiocarcinoma interstitial fluid. Proteins derived from three samples of tumor interstitial fluid and paired samples of adjacent normal interstitial fluid from cholangiocarcinoma patients were subjected to two-dimensional liquid chromatography with tandem mass spectrometry. Candidate proteins were selected based on a greater than twofold change in expression levels between tumor interstitial fluid and normal interstitial fluid...
April 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29617057/antigen-specific-helios-neuropilin-1-tregs-induce-apoptosis-of-autoreactive-b-cells-via-pd-l1
#8
Janine Gotot, Ermanila Dhana, Hideo Yagita, Romina Kaiser, Isis Ludwig-Portugall, Christian Kurts
Regulatory T cells (Tregs) maintain self-tolerance and prevent autoimmunity by controlling autoreactive T cells. We recently demonstrated in vivo that Tregs can directly suppress auto-reactive B cells via programmed death ligand 1 (PD-L1) that ligated PD-1 on B cells and caused them to undergo apoptosis. Here we asked whether this mechanism is utilized by thymus-derived natural Tregs and/or by peripheral lymphoid tissue-induced Tregs. We first demonstrated that antigen-specific PD-L1-expressing Tregs were induced in the draining lymph node (LN) of autoantigen-expressing tissue and characterized them by their lack of the transcription factor Helios and of the surface marker Neuropilin-1 (Nrp-1)...
April 4, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29549139/neuropilin-1-expression-in-adipose-tissue-macrophages-protects-against-obesity-and-metabolic-syndrome
#9
Ariel Molly Wilson, Zhuo Shao, Vanessa Grenier, Gaëlle Mawambo, Jean-François Daudelin, Agnieszka Dejda, Frédérique Pilon, Natalija Popovic, Salix Boulet, Célia Parinot, Malika Oubaha, Nathalie Labrecque, Vincent de Guire, Mathieu Laplante, Guillaume Lettre, Florian Sennlaub, Jean-Sebastien Joyal, Michel Meunier, Przemyslaw Sapieha
Obesity gives rise to metabolic complications by mechanisms that are poorly understood. Although chronic inflammatory signaling in adipose tissue is typically associated with metabolic deficiencies linked to excessive weight gain, we identified a subset of neuropilin-1 (NRP1)-expressing myeloid cells that accumulate in adipose tissue and protect against obesity and metabolic syndrome. Ablation of NRP1 in macrophages compromised lipid uptake in these cells, which reduced substrates for fatty acid β-oxidation and shifted energy metabolism of these macrophages toward a more inflammatory glycolytic metabolism...
March 16, 2018: Science Immunology
https://www.readbyqxmd.com/read/29543041/neuropilin-1and-platelet-derived-growth-factor-receptors-cooperatively-regulate-intermediate-filaments-and-mesenchymal-cell-migration-during-alveolar-septation
#10
Stephen E McGowan, Diann M McCoy
Secondary alveolar septa are mostly generated after birth in humans and in mice this is completely accomplished postnatally, when mechanical stresses vary as airspace pressure oscillates. Alveolar mesenchymal cells deposit elastic fibers which limit cellular strain, but while the elastic fiber network is incomplete, this function is also served by the intracellular cytoskeleton. Intermediate filament proteins support deformation during cellular division and migration, which occur during septal elongation. Because platelet-derived growth factor-alpha (PDGFRα) signaling is essential for alveolar septation, we hypothesized that neuropilin-1 (NRP1) may link PDGFRα to cytoskeletal deformation...
March 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29535768/neuropilin-1-mediates-keratinocyte-growth-factor-signaling-in-adipose-derived-stem-cells-potential-involvement-in-adipogenesis
#11
Simona Ceccarelli, Cristina Nodale, Enrica Vescarelli, Paola Pontecorvi, Valeria Manganelli, Giovanni Casella, Maria Giuseppina Onesti, Maurizio Sorice, Ferdinando Romano, Antonio Angeloni, Cinzia Marchese
Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29532881/vegf-pathway-targeting-drugs-induce-evasive-adaptation-by-activation-of-neuropilin-1-cmet-in-colon-cancer-cells
#12
Chisato Tomida, Naoko Yamagishi, Hikaru Nagano, Takayuki Uchida, Ayako Ohno, Katsuya Hirasaka, Takeshi Nikawa, Shigetada Teshima-Kondo
Anti-angiogenic therapies targeting vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) are important treatments for a number of human malignancies, including colorectal cancers. However, there is increasing evidence that VEGF/VEGF-R inhibitors promote the adaptive and evasive resistance of tumor cells to the therapies. The mechanism by which the cancer cells become resistant remains unclear. One potential mechanism is that VEGF/VEGF-R blockers directly act on tumor cells independently of anti-angiogenic effects...
April 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29486132/the-role-of-neuropilin-1-fyn-interaction-in-odontoblast-differentiation-of-dental-pulp-stem-cells
#13
Yihua Song, Peipei Cao, Zhifeng Gu, Jingwen Xiao, Min Lian, Dan Huang, Jing Xing, Ye Zhang, Xingmei Feng, Chenfei Wang
Abnormal odontoblast differentiation of dental pulp stem cells (DPSCs) caused by inflammation is closely related to the development of dental caries. Neuropilin-1 (NRP1) is one of the members of neuropilin family. It can combine with disparate ligands involved in regulating cell differentiation. FYN belongs to the protein-tyrosine kinase family, which has been implicated in the control of cell growth, and the effect can be further strengthened by inflammatory factors. In our studies, we verified that NRP1 can form complexes with FYN and have the correlation changes in odontoblast differentiation of DPSCs...
February 27, 2018: Cellular Reprogramming
https://www.readbyqxmd.com/read/29471421/class-3-semaphorins-modulate-the-invasive-capacity-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#14
Man Wai Tang, Beatriz Malvar Fernández, Simon P Newsom, Jaap D van Buul, Timothy R D J Radstake, Dominique L Baeten, Paul P Tak, Kris A Reedquist, Samuel García
Objective: Class 3 semaphorins regulate diverse cellular processes relevant to the pathology of RA, including immune modulation, angiogenesis, apoptosis and invasive cell migration. Therefore, we analysed the potential role of class 3 semaphorins in the pathology of RA. Methods: Protein and mRNA expression in RA synovial tissue, SF and fibroblast-like synoviocytes (FLS) were determined by immunoblotting and quantitative PCR (qPCR). RA FLS migration and invasion were determined using wound closure and transwell invasion assays, respectively...
February 19, 2018: Rheumatology
https://www.readbyqxmd.com/read/29458191/a-novel-neuropilin-1-binding-sequence-in-the-human-t-cell-lymphotropic-virus-type-1-envelope-glycoprotein
#15
Hideki Kusunoki, Toshiyuki Tanaka, Toshiyuki Kohno, Kazuhiko Matsuhashi, Kazuo Hosoda, Kaori Wakamatsu, Isao Hamaguchi
Entry of human T-cell lymphotropic virus type 1 (HTLV-1) into host cells is mainly mediated by interactions between the viral envelope glycoprotein surface unit (SU) and three host receptors: glucose transporter type 1, heparin/heparan sulfate proteoglycan, and neuropilin-1 (Nrp1). Here, we analyzed the interaction between HTLV-1 SU and Nrp1 using nuclear magnetic resonance and isothermal titration calorimetry. We found that two SU peptides, residues 85-94 and residues 304-312, bound directly to the Nrp1 b1 domain with affinities of 7...
February 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29457830/mirna-124-3p-neuropilin-1-nrp-1-axis-plays-an-important-role-in-mediating-glioblastoma-growth-and-angiogenesis
#16
Guilong Zhang, Lukui Chen, Ahsan Ali Khan, Bingqian Li, Bin Gu, Fan Lin, Xinhui Su, Jianghua Yan
Glioblastoma Multiforme (GBM) is the most lethal brain malignancy which involves multi-gene abnormality. Unfortunately, effective therapy against GBM is still lacking. Previously, we found that NRP-1 and its downstream NRP-1/GIPC1 pathway played an important role in GBM. In this study, we further investigated the upstream signaling of NRP-1 to understand how it is regulated. Firstly, we identified that hsa-miR-124-3p was miRNA differentially expressed in GBM and in normal brain tissues by high-throughput sequencing...
February 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29435012/microrna-9-functions-as-a-tumor-suppressor-and-enhances-radio-sensitivity-in-radio-resistant-a549-cells-by-targeting-neuropilin-1
#17
Kai Xiong, Li Hong Shao, Hai Qin Zhang, Linlin Jin, Wei Wei, Zhuo Dong, Yue Quan Zhu, Ning Wu, Shun Zi Jin, Li Xiang Xue
Radiotherapy is commonly used to treat lung cancer but may not kill all cancer cells, which may be attributed to the radiotherapy resistance that often occurs in non-small cell lung cancer (NSCLC). At present, the molecular mechanism of radio-resistance remains unclear. Neuropilin 1 (NRP1), a co-receptor for vascular endothelial growth factor (VEGF), was demonstrated to be associated with radio-resistance of NSCLC cells via the VEGF-phosphoinositide 3-kinase-nuclear factor-κB pathway in our previous study...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434931/neuropilin-1-promotes-primary-liver-cancer-progression-by-potentiating-the-activity-of-hepatic-stellate-cells
#18
Zhi-Chao Xu, Hao-Xin Shen, Chen Chen, Li Ma, Wen-Zhi Li, Lin Wang, Zhi-Min Geng
As a co-receptor for a variety of cytokines, neuropilin-1 (NRP-1) is detectable in primary liver cancer (PLC) cells. Previous studies determined that silencing of NRP-1 expression attenuated the proliferation, migration and invasion of PLC cells. An increasing number of studies have highlighted the crucial role of the tumor microenvironment in the pathogenesis of cancer. Hepatic stellate cells (HSCs) are one of the major interstitial cell types present in the liver tumor microenvironment, and can promote the proliferation, migration and invasion of PLC cells...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29432830/functional-polymorphisms-of-the-neuropilin-1-gene-are-associated-with-the-risk-of-tetralogy-of-fallot-in-a-chinese-han-population
#19
Sai-Hou Fan, Zhen-Ya Shen, Yi-Min Xiao
Tetralogy of Fallot (TOF) is one of the most severe forms of cyanotic congenital heart disease (CHD) and is also the most common. Previous genome-wide association study (GWAS) and replication studies have suggested that a polymorphism in the neuropilin 1 (NRP1) gene is significantly associated with the risk of TOF. To further confirm the association between the NRP1 polymorphism and the risk of TOF and to identify additional positive functional single-nucleotide polymorphisms (SNPs) for TOF risk, we systematically screened for functional polymorphisms throughout the regulatory and coding regions of the NRP1 gene...
February 9, 2018: Gene
https://www.readbyqxmd.com/read/29430837/architecture-and-hydration-of-the-arginine-binding-site-of-neuropilin-1
#20
Filipa Mota, Constantina Fotinou, Rohini Rhana, A W Edith Chan, Tamas Yelland, Mohamed T Arooz, Andrew P O'Leary, Jennie Hutton, Paul Frankel, Ian Zachary, David Selwood, Snezana Djordjevic
Neuropilin-1 (NRP1) is a transmembrane co-receptor involved in binding interactions with variety of ligands and receptors, including receptor tyrosine kinases. Expression of NRP1 in several cancers correlates with cancer stages and poor prognosis. Thus, NRP1 has been considered a therapeutic target and is the focus of multiple drug discovery initiatives. Vascular endothelial growth factor (VEGF) binds to the b1 domain of NRP1 through interactions between the C-terminal arginine of VEGF and residues in the NRP1 binding site including Tyr297, Tyr353, Asp320, Ser346, and Thr349...
February 12, 2018: FEBS Journal
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