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https://www.readbyqxmd.com/read/27921359/modulation-of-vegf-signaling-in-a-mouse-model-of-diabetes-by-xanthohumol-and-8-prenylnaringenin-unveiling-the-angiogenic-paradox-and-metabolism-interplay
#1
Raquel Costa, Ilda Rodrigues, Luísa Guardão, Joana Quelhas Lima, Emília Sousa, Raquel Soares, Rita Negrão
SCOPE: Imbalance in kidney and heart neovascularization is common in type2 Diabetes (T2DM) patients. Nevertheless, the mechanisms governing this angiogenic paradox have not been elucidated. Xanthohumol (XN) and 8-prenylnaringenin (8PN) beer polyphenols modulate angiogenesis, being thus targets for T2DM-related complications. Our work examined whether polyphenols consumption affects angiogenic paradox and metabolism in a T2DM mouse model. METHODS AND RESULTS: An increase in kidney and a reduction in left ventricle (LV) microvessels of diabetic C57Bl/6 mice were observed...
December 6, 2016: Molecular Nutrition & Food Research
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/27906605/current-drug-design-to-target-the-semaphorin-neuropilin-plexin-complexes
#3
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/27895796/promotion-of-metastasis-of-thyroid-cancer-cells-via-nrp-2-mediated-induction
#4
Dom-Gene Tu, Wen-Wei Chang, Ming-Shiou Jan, Chi-Wen Tu, Yin-Che Lu, Chien-Kuo Tai
Tumor-node-metastasis is one of the leading causes of morbidity and mortality in thyroid cancer patients. Upregulation of vascular endothelial growth factor-C (VEGF-C) increases the migratory ability of thyroid cancer cells to lymph nodes. Expression of neuropilin-2 (NRP-2), the co-receptor of VEGF-C, has been reported to be correlated with lymph node metastasis in human thyroid cancer. The present study investigated the role of VEGF-C/NRP-2 signaling in the regulation of metastasis of two different types of human thyroid cancer cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27889287/structure-activity-relationship-study-of-a-small-cyclic-peptide-h-c-lys-pro-glu-arg-oh-a-potent-inhibitor-of-vascular-endothelial-growth-factor-interaction-with-neuropilin-1
#5
Karolina Grabowska, Anna K Puszko, Piotr F J Lipiński, Anna K Laskowska, Beata Wileńska, Ewa Witkowska, Gerard Y Perret, Aleksandra Misicka
Inhibition of angiogenesis is one of the most promising approaches in anticancer therapy. It was recently suggested that Neuropilin-1 (NRP-1) in tumour cells may serve as a separate receptor for Vascular Endothelial Growth Factor-165 (VEGF165) which is one of the main pro-angiogenic agents in the organism. Therefore molecules inhibiting VEGF165 binding to NRP-1 could be potential candidates for new antiangiogenic and anticancer drugs. Here we present a structure-activity relationship study of the peptide H-c[Lys-Pro-Glu]-Arg-OH which showed high inhibitory effect on VEGF165/NRP-1 binding (IC50=0...
November 14, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27880905/semaphorin-3g-provides-a-repulsive-guidance-cue-to-lymphatic-endothelial-cells-via-neuropilin-2-plexind1
#6
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/27879479/identify-signature-regulatory-network-for-glioblastoma-prognosis-by-integrative-mrna-and-mirna-co-expression-analysis
#7
Zhi-Tong Bing, Guang-Hui Yang, Jie Xiong, Ling Guo, Lei Yang
Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor in adults. Patients with this disease have a poor prognosis. The objective of this study is to identify survival-related individual genes (or miRNAs) and miRNA -mRNA pairs in GBM using a multi-step approach. First, the weighted gene co-expression network analysis and survival analysis are applied to identify survival-related modules from mRNA and miRNA expression profiles, respectively. Subsequently, the role of individual genes (or miRNAs) within these modules in GBM prognosis are highlighted using survival analysis...
December 2016: IET Systems Biology
https://www.readbyqxmd.com/read/27863391/nordihydroguaiaretic-acid-impairs-prostate-cancer-cell-migration-and-tumor-metastasis-by-suppressing-neuropilin-1
#8
Xin Li, Shengjun Fan, Xueyang Pan, Yilixiati Xiaokaiti, Jianhui Duan, Yundi Shi, Yan Pan, Lu Tie, Xin Wang, Yuhua Li, Xuejun Li
Tumor metastasis is a major cause leading to the deaths of cancer patients. Nordihydroguaiaretic acid (NDGA) is a natural product that has been demonstrated to show therapeutic values in multiple diseases. In this study, we report that NDGA can inhibit cell migration and tumor metastasis via a novel mechanism. NDGA suppresses NRP1 function by downregulating its expression, which leads to attenuated cell motility, cell adhesion to ECM and FAK signaling in cancer cells. Moreover, due to its cross-cell type activity on NRP1 suppression, NDGA also impairs angiogenesis function of endothelial cells and fibronectin assembly by fibroblasts, both of which are critical to promote metastasis...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27858201/semaphorin3a-neuropilin1-signalling-is-involved-in-the-generation-of-cortical-interneurons
#9
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
#10
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/27853189/a-multiscale-computational-model-predicts-distribution-of-anti-angiogenic-isoform-vegf165b-in-peripheral-arterial-disease-in-human-and-mouse
#11
Liang-Hui Chu, Vijay Chaitanya Ganta, Min H Choi, George Chen, Stacey D Finley, Brian H Annex, Aleksander S Popel
Angiogenesis is the growth of new blood vessels from pre-existing microvessels. Peripheral arterial disease (PAD) is caused by atherosclerosis that results in ischemia mostly in the lower extremities. Clinical trials including VEGF-A administration for therapeutic angiogenesis have not been successful. The existence of anti-angiogenic isoform (VEGF165b) in PAD muscle tissues is a potential cause for the failure of therapeutic angiogenesis. Experimental measurements show that in PAD human muscle biopsies the VEGF165b isoform is at least as abundant if not greater than the VEGF165a isoform...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27844052/neuropilin-1-and-the-positions-of-glomeruli-in-the-mouse-olfactory-bulb
#12
Bolek Zapiec, Olaf Christian Bressel, Mona Khan, Andreas Walz, Peter Mombaerts
It is known since 1996 that mouse odorant receptors (ORs) are involved in determining the positions of the sites of coalescence of axons of olfactory sensory neurons (OSNs)-the thousands of glomeruli in the olfactory bulb. But the molecular and cellular mechanisms of OR-mediated axonal coalescence into glomeruli remain unclear. A model was proposed in 2006-2009 whereby OR-derived cAMP signals, rather than direct action of OR molecules, determine the target destinations (glomeruli) of OSNs in the bulb. This model hypothesizes that OR-derived cAMP signals determine the expression levels of neuropilin 1 (Nrp1) in OSN axon termini; that levels of Nrp1 in glomeruli form a gradient from anterior-low to posterior-high throughout the bulb; and that these Nrp1 levels mechanistically determine anterior-posterior patterning of glomeruli...
September 2016: ENeuro
https://www.readbyqxmd.com/read/27835904/tuftsin-prevents-the-negative-immunoregulation-of-neuropilin-1highcd4-cd25-regulatory-t-cells-and-improves-survival-rate-in-septic-mice
#13
Yu-Lei Gao, Mu-Ming Yu, Song-Tao Shou, Ying Yao, Yan-Cun Liu, Li-Jun Wang, Bin Lu, Yan-Fen Chai
Our previous research showed that neuropilin (Nrp) -1highCD4+CD25+Regulatory T cells (Tregs) exhibited primary negative immunoregulation in sepsis induced immune dysfunction. Tuftsin is the typical ligand of Nrp-1. Herein, we investigated the potential therapeutic value and mechanisms of tuftsin in sepsis. Sepsis per se markedly decreased the serum concentration of tuftsin, administration of tuftsin improved the survival rate of septic mice with cecal ligation and puncture (CLP). In vitro study, tuftsin prevented the negative immunoregulation of Nrp-1highCD4+CD25+Tregs, including weakening the expression of forkhead/winged helix transcription factor (Foxp)- 3/cytotoxic T lymphocyte associated antigen (CTLA)-4, inhibiting the secretion of transforming growth factor (TGF)-β, and weakening the immunosuppressive function of Nrp-1highCD4+CD25+Tregs to conventional CD4+CD25-T cells...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27834687/endothelial-scube2-interacts-with-vegfr2-and-regulates-vegf-induced-angiogenesis
#14
Yuh-Charn Lin, Tsu-Yi Chao, Chi-Tai Yeh, Steve R Roffler, Reiji Kannagi, Ruey-Bing Yang
OBJECTIVE: Vascular endothelial growth factor (VEGF), a major mediator of angiogenesis, exerts its proangiogenic action by binding to VEGFR2 (VEGF receptor 2), the activity of which is further modulated by VEGFR2 coreceptors such as neuropilins. However, whether VEGFR2 is regulated by additional coreceptors is not clear. To investigate whether SCUBE2 (signal peptide-CUB-EGF domain-containing protein 2), a peripheral membrane protein expressed in vascular endothelial cells (ECs) known to bind other signaling receptors, functions as a VEGFR2 coreceptor and to verify the role of SCUBE2 in the VEGF-induced angiogenesis...
November 10, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27815442/vegf-requires-the-receptor-nrp-1-to-inhibit-lipopolysaccharide-dependent-dendritic-cell-maturation
#15
Nougboli A E Oussa, Amina Dahmani, Marie Gomis, Manon Richaud, Emil Andreev, Ali-Reza Navab-Daneshmand, Julie Taillefer, Cédric Carli, Salix Boulet, Laurent Sabbagh, Nathalie Labrecque, Przemyslaw Sapieha, Jean-Sébastien Delisle
To stimulate a productive T cell response, dendritic cells (DC) must undergo maturation characterized by heightened cell surface expression of MHC and costimulatory molecules as well as cytokine production. Conversely, the inhibition of DC maturation is a central mechanism of immune tolerance. The control of the DC maturation process relies on the integration of several cellular stimulatory or inhibitory signals. The soluble factors and their receptors controlling this central aspect of DC biology are incompletely characterized...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27803667/wedelolactone-enhances-osteoblastogenesis-but-inhibits-osteoclastogenesis-through-sema3a-nrp1-plexina1-pathway
#16
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/27798666/a-novel-physiological-glycosaminoglycan-deficient-splice-variant-of-neuropilin-1-is-anti-tumorigenic-in-vitro-and-in-vivo
#17
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
https://www.readbyqxmd.com/read/27797376/co-targeting-of-egf-receptor-and-neuropilin-1-overcomes-cetuximab-resistance-in-pancreatic-ductal-adenocarcinoma-with-integrin-%C3%AE-1-driven-src-akt-bypass-signaling
#18
Y-J Kim, K Jung, D-S Baek, S-S Hong, Y-S Kim
Pancreatic ductal adenocarcinoma (PDAC) cells usually overexpress the epidermal growth factor receptor (EGFR); however, most are resistant to the anti-EGFR monoclonal antibody, cetuximab. In this study, we report that the molecular mechanism of resistance to cetuximab in PDAC cells is mediated by the overexpression of active integrin β1 with downstream Src-Akt activation; this triggers an EGFR ligand-independent proliferation signaling, bypassing EGFR-blocking effect. Knockdown of integrin β1 or inhibition of Src or Akt sensitized cetuximab-resistant (Ctx(R)) PDAC cells to cetuximab...
October 31, 2016: Oncogene
https://www.readbyqxmd.com/read/27797175/liposome-based-systemic-glioma-targeted-drug-delivery-enabled-by-all-d-peptides
#19
Man Ying, Changyou Zhan, Songli Wang, Bingxin Yao, Xuefeng Hu, Xianfei Song, Mingfei Zhang, Xiaoli Wei, Yan Xiong, Weiyue Lu
As the most aggressive brain tumor, chemotherapy of malignant glioma remains to be extremely challenging in clinic. The blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) are physiological and pathological barriers preventing therapeutic drugs from reaching the glioma region. In addition, vasculogenic mimicry (VM) formed by invasive glioma cells instead of endothelial cells and angiogenesis are very common in glioma, leading to the poor prognosis and recurrence of glioma. An ideal drug delivery system for glioma chemotherapy needs to traverse the BBB and BBTB and then target VM, angiogenesis, and glioma cells...
October 31, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27791986/human-airway-smooth-muscle-cell-proliferation-from-asthmatics-is-negatively-regulated-by-semaphorin3a
#20
Hesam Movassagh, Nazanin Tatari, Lianyu Shan, Latifa Koussih, Duaa Alsubait, Mahdi Khattabi, Naresh S Redhu, Michael Roth, Michael Tamm, Jamila Chakir, Abdelilah S Gounni
Airway smooth muscle (ASM) hyperplasia is a key feature of airway remodeling in development of lung diseases such as asthma. Anomalous proliferation of ASM cells directly contributes to ASM hyperplasia. However, the molecular mechanisms controlling ASM cell proliferation are not completely understood. Semaphorins are versatile regulators of various cellular processes including cell growth and proliferation. The role of semaphorins in ASM cell proliferation has remained to be addressed. Here, we report that semaphorin 3A (Sema3A) receptor, neuropilin 1 (Nrp1), is expressed on human ASM cells (HASMC) isolated from healthy and asthmatic donors and treatment of these cells with exogenous Sema3A inhibits growth factor-induced proliferation...
October 25, 2016: Oncotarget
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