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https://www.readbyqxmd.com/read/28319199/a-computational-analysis-of-in-vivo-vegfr-activation-by-multiple-co-expressed-ligands
#1
Lindsay E Clegg, Feilim Mac Gabhann
The splice isoforms of vascular endothelial growth A (VEGF) each have different affinities for the extracellular matrix (ECM) and the coreceptor NRP1, which leads to distinct vascular phenotypes in model systems expressing only a single VEGF isoform. ECM-immobilized VEGF can bind to and activate VEGF receptor 2 (VEGFR2) directly, with a different pattern of site-specific phosphorylation than diffusible VEGF. To date, the way in which ECM binding alters the distribution of isoforms of VEGF and of the related placental growth factor (PlGF) in the body and resulting angiogenic signaling is not well-understood...
March 20, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28270793/expression-of-semaphorins-neuropilins-vegf-and-tenascins-in-rat-and-human-primary-sensory-neurons-after-a-dorsal-root-injury
#2
Tomas Lindholm, Mårten Risling, Thomas Carlstedt, Henrik Hammarberg, Wilhelm Wallquist, Staffan Cullheim, Mattias K Sköld
Dorsal root injury is a situation not expected to be followed by a strong regenerative growth, or growth of the injured axon into the central nervous system of the spinal cord, if the central axon of the dorsal root is injured but of strong regeneration if subjected to injury to the peripherally projecting axons. The clinical consequence of axonal injury is loss of sensation and may also lead to neuropathic pain. In this study, we have used in situ hybridization to examine the distribution of mRNAs for the neural guidance molecules semaphorin 3A (SEMA3A), semaphorin 3F (SEMA3F), and semaphorin 4F (SEMA4F), their receptors neuropilin 1 (NP1) and neuropilin 2 (NP2) but also for the neuropilin ligand vascular endothelial growth factor (VEGF) and Tenascin J1, an extracellular matrix molecule involved in axonal guidance, in rat dorsal root ganglia (DRG) after a unilateral dorsal rhizotomy (DRT) or sciatic nerve transcetion (SNT)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28262664/motor-neurons-control-blood-vessel-patterning-in-the-developing-spinal-cord
#3
Patricia Himmels, Isidora Paredes, Heike Adler, Andromachi Karakatsani, Robert Luck, Hugo H Marti, Olga Ermakova, Eugen Rempel, Esther T Stoeckli, Carmen Ruiz de Almodóvar
Formation of a precise vascular network within the central nervous system is of critical importance to assure delivery of oxygen and nutrients and for accurate functionality of neuronal networks. Vascularization of the spinal cord is a highly stereotypical process. However, the guidance cues controlling blood vessel patterning in this organ remain largely unknown. Here we describe a new neuro-vascular communication mechanism that controls vessel guidance in the developing spinal cord. We show that motor neuron columns remain avascular during a developmental time window, despite expressing high levels of the pro-angiogenic vascular endothelial growth factor (VEGF)...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28260064/tumor-penetrating-peptide-fused-to-a-pro-apoptotic-peptide-facilitates-effective-gastric-cancer-therapy
#4
Ying Huang, Xihan Li, Huizi Sha, Lianru Zhang, Xinyu Bian, Xiao Han, Baorui Liu
KLA (sequence, KLAKLAKKLAKLAK) is a peptide which leads to programmed cell death by disrupting the mitochondrial membrane. However, low penetration in tumors greatly limits its application and efficacy. To develop a KLA-based cancer therapy, KLA-iRGD, a recombinant protein was constructed. It consists of the KLA peptide and iRGD (CRGDKGPDC), a tumor-homing peptide with high penetration into tumor tissue and cells. The conjugated KLA exhibits pro-apoptotic activity to prevent the growth of a tumor once it is inside the cell...
February 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28257831/silencing-of-galectin-1-inhibits-retinal-neovascularization-and-ameliorates-retinal-hypoxia-in-a-murine-model-of-oxygen-induced-ischemic-retinopathy
#5
Ning Yang, Wenxi Zhang, Tao He, Yiqiao Xing
Aberrant neovascularization is a consequence of inappropriate angiogenic signaling and contributes to several diseases. Although many regulators of pathogenic angiogenesis have been identified, the understanding of this process remains incomplete. Galectin-1 (Gal-1), as a homodimeric protein with a single carbohydrate-recognition domain, is implicated in several pathologic processes, including angiogenesis; however, its involvement in retinal neovascularization (RNV) remains unknown. Here, we investigated the anti-angiogenic effect of silencing Gal-1 through intravitreal injection in a mouse model of oxygen-induced retinopathy (OIR)...
February 28, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28255116/-nrp-1-expression-in-healing-process-of-traumatic-brain-injury-combined-with-tibial-fracture
#6
Zhengzheng Li, Junwei Zhao, Wei Luo, Kang Li, Shuanhu Lei, Yuliang Wang
To examine the expression of neuropilin-1 (Nrp-1), semaphorin 3A (Sema3A) and vascular endothelial growth factor (VEGF) in the healing process of tibial fracture after traumatic brain injury and to explore the mechanism of Nrp-1 in the formation of pathological callus after nerve injury.
 Methods: A total of 192 Wister female rats, 8-10 weeks old and weighing 220-250 g, were randomly divided into a control group (Group C), a tibia fracture group (Group F), a traumatic brain injury group (Group TBI), a traumatic brain injury combined with the tibia fracture group (Group TBI+F) (n=48 in each group)...
February 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28254885/neuropilin-1-binds-platelet-derived-growth-factor-pdgf-d-and-is-a-co-receptor-in-pdgf-d-pdgf-receptor-%C3%AE-signaling
#7
Lars Muhl, Erika Bergsten Folestad, Hanna Gladh, Yixin Wang, Christine Moessinger, Lars Jakobsson, Ulf Eriksson
Platelet-derived growth factor (PDGF)-D is a PDGF receptor β (PDGFRβ) specific ligand implicated in a number of pathological conditions, such as cardiovascular disease and cancer, but its biological function remains incompletely understood.In this study, we demonstrate that PDGF-D binds directly to NRP1, with the requirement of the C-terminal Arg residue of PDGF-D. Stimulation with PDGF-D, but not PDGF-B, induced PDGFRβ/NRP1 complex formation in fibroblasts. Additionally, PDGF-D induced translocation of NRP1 to cell-cell junctions in endothelial cells, independent of PDGFRβ, altering the availability of NRP1 for VEGF-A/VEGF receptor 2 signaling...
March 2, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28254884/a-functional-coupling-between-crmp1-and-nav1-7-for-retrograde-propagation-of-semaphorin3a-signaling
#8
Masayuki Yamane, Naoya Yamashita, Tomonobu Hida, Yoshinori Kamiya, Fumio Nakamura, Pappachan Kolattukudy, Yoshio Goshima
Semaphorin3A (Sema3A) is a secreted type of axon guidance molecules that regulates axon wiring through neuropilin-1 (NRP1) and PlexinAs (PlexAs) receptor complex. Sema3A regulates the dendritic branching through a tetrodotoxin (TTX)-sensitive retrograde axonal transport of PlexAs and Tropomyosin-related kinase A (TrkA) complex. We here demonstrate that Nav1.7, a TTX-sensitive Na(+) channel, by coupling with collapsin response mediator protein 1 (CRMP1), mediates the Sema3A-induced retrograde transport. In mouse dorsal root ganglion (DRG) neurons, Sema3A increased co-localization of PlexA4 and TrkA in the growth cones and axons...
March 2, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28199847/neuropilin-1-is-expressed-on-lymphoid-tissue-residing-lti-like-group-3-innate-lymphoid-cells-and-associated-with-ectopic-lymphoid-aggregates
#9
Medya Mara Shikhagaie, Åsa K Björklund, Jenny Mjösberg, Jonas S Erjefält, Anne S Cornelissen, Xavier Romero Ros, Suzanne M Bal, Jasper J Koning, Reina E Mebius, Michiko Mori, Melanie Bruchard, Bianca Blom, Hergen Spits
Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1(+) group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1(+) ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28194441/deletion-of-neuropilin-2-enhances-detrusor-contractility-following-bladder-outlet-obstruction
#10
Evalynn Vasquez, Vivian Cristofaro, Stefan Lukianov, Fiona C Burkhard, Ali Hashemi Gheinani, Katia Monastyrskaya, Diane R Bielenberg, Maryrose P Sullivan, Rosalyn M Adam
Chronic urethral obstruction and the ensuing bladder wall remodeling can lead to diminished bladder smooth muscle (BSM) contractility and debilitating lower urinary tract symptoms. No effective pharmacotherapy exists to restore BSM contractile function. Neuropilin 2 (Nrp2) is a transmembrane protein that is highly expressed in BSM. Nrp2 deletion in mice leads to increased BSM contraction. We determined whether genetic ablation of Nrp2 could restore BSM contractility following obstruction. Partial bladder outlet obstruction (pBOO) was created by urethral occlusion in mice with either constitutive and ubiquitous, or inducible smooth muscle-specific deletion of Nrp2, and Nrp2-intact littermates...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28107458/neuropilin-1-involvement-in-choroidal-and-retinal-neovascularisation
#11
Patricia Fernández-Robredo, Senthil Selvam, Michael B Powner, Dawn A Sim, Marcus Fruttiger
PURPOSE: Inhibiting VEGF is the gold standard treatment for neovascular age-related macular degeneration (AMD). It is also effective in preventing retinal oedema and neovascularisation (NV) in diabetic retinopathy (DR) and retinal vein occlusions (RVO). Neuropilin 1 (Nrp1) is a co-receptor for VEGF and many other growth factors, and therefore a possible alternative drug target in intra ocular neovascular disease. Here we assessed choroidal and retinal NV in an inducible, endothelial specific knock out model for Nrp1...
2017: PloS One
https://www.readbyqxmd.com/read/28103506/the-effect-of-anti-angiogenic-drugs-on-regulatory-t-cells-in-the-tumor-microenvironment
#12
REVIEW
Chenxi Hu, Xiaodong Jiang
A benefit of anti-angiogenic drugs is improved tumor immune tolerance. Regulatory T cells (Tregs) in the tumor microenvironment mediate tumor immune tolerance and anti-angiogenic drugs not only indirectly affect Tregs via dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) but they can also act directly on Tregs causing immunosuppression. Specifically, these drugs may induce differentiation and chemotaxis and reduce the number and function of Tregs by targeting vascular endothelial growth factor receptor 2 (VEGFR-2) and neuropilin-1 (NRP-1) on the cell surface...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28098756/detection-of-the-vascular-endothelial-growth-factor-with-a-novel-bioluminescence-resonance-energy-transfer-pair-using-a-two-component-system
#13
Tobias Wimmer, Eva Schroeter, Birgit Lorenz, Knut Stieger
In this paper we describe a two-component BRET (bioluminescence resonance energy transfer)-based method to detect vascular endothelial growth factor (VEGF) molecules in unknown samples as the basis for subsequent in vivo use. A luminescent VEGF binding molecule, which binds in the receptor binding motif of VEGF, is used as the energy donor, transferred to a fluorophore-coupled VEGF binding molecule (acceptor), which binds to the neuropilin binding motif of VEGF, thus enabling energy transfer from the donor to the acceptor molecule...
January 13, 2017: Sensors
https://www.readbyqxmd.com/read/28096505/the-neuropilin-2-isoform-nrp2b-uniquely-supports-tgf%C3%AE-mediated-progression-in-lung-cancer
#14
Robert M Gemmill, Patrick Nasarre, Joyce Nair-Menon, Federico Cappuzzo, Lorenza Landi, Armida D'Incecco, Hidetaka Uramoto, Takeshi Yoshida, Eric B Haura, Kent Armeson, Harry A Drabkin
Neuropilins (NRP1 and NRP2) are co-receptors for heparin-binding growth factors and class 3 semaphorins. Different isoforms of NRP1 and NRP2 are produced by alternative splicing. We found that in non-small cell lung cancer (NSCLC) cell lines, transforming growth factor-β (TGFβ) signaling preferentially increased the abundance of NRP2b. NRP2b and NRP2a differ only in their carboxyl-terminal regions. Although the presence of NRP2b inhibited cultured cell proliferation and primary tumor growth, NRP2b enhanced cellular migration, invasion into Matrigel, and tumorsphere formation in cultured cells in response to TGFβ signaling and promoted metastasis in xenograft mouse models...
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28092670/neuropilin-1-is-upregulated-in-the-adaptive-response-of-prostate-tumors-to-androgen-targeted-therapies-and-is-prognostic-of-metastatic-progression-and-patient-mortality
#15
B W C Tse, M Volpert, E Ratther, N Stylianou, M Nouri, K McGowan, M L Lehman, S J McPherson, M Roshan-Moniri, M S Butler, J Caradec, C Y Gregory-Evans, J McGovern, R Das, M Takhar, N Erho, M Alshalafa, E Davicioni, E M Schaeffer, R B Jenkins, A E Ross, R J Karnes, R B Den, L Fazli, P A Gregory, M E Gleave, E D Williams, P S Rennie, R Buttyan, J H Gunter, L A Selth, P J Russell, C C Nelson, B G Hollier
Recent evidence has implicated the transmembrane co-receptor neuropilin-1 (NRP1) in cancer progression. Primarily known as a regulator of neuronal guidance and angiogenesis, NRP1 is also expressed in multiple human malignancies, where it promotes tumor angiogenesis. However, non-angiogenic roles of NRP1 in tumor progression remain poorly characterized. In this study, we define NRP1 as an androgen-repressed gene whose expression is elevated during the adaptation of prostate tumors to androgen-targeted therapies (ATTs), and subsequent progression to metastatic castration-resistant prostate cancer (mCRPC)...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28091556/vegf-b-promotes-recovery-of-corneal-innervations-and-trophic-functions-in-diabetic-mice
#16
Guohu Di, Xiaowen Zhao, Xia Qi, Songmei Zhang, Lu Feng, Weiyun Shi, Qingjun Zhou
Vascular endothelial growth factor (VEGF)-B possesses the capacity of promoting injured peripheral nerve regeneration and restore their sensory and trophic functions. However, the contribution and mechanism of VEGF-B in diabetic peripheral neuropathy remains unclear. In the present study, we investigated the expression and role of VEGF-B in diabetic corneal neuropathy by using type 1 diabetic mice and cultured trigeminal ganglion (TG) neurons. Hyperglycemia attenuated the endogenous expression of VEGF-B in regenerated diabetic corneal epithelium, but not that of VEGF receptors in diabetic TG neurons and axons...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28079897/tsc1-expression-by-dendritic-cells-is-required-to-preserve-t-cell-homeostasis-and-response
#17
Yuechen Luo, Wenwen Li, Gang Yu, Juan Yu, Ling Han, Ting Xue, Zhina Sun, Song Chen, Chunming Fang, Chunxiao Zhao, Qing Niu, Fei Yang, Zhongchao Han, Tao Cheng, Yun Zeng, Fang Liao, Guogang Xu, Xiaoming Feng
Dendritic cells (DCs) are pivotal to the induction of adaptive T-cell immune responses. Recent evidence highlights a critical role of tuberous sclerosis complex 1 (Tsc1), a primarily upstream negative regulator of mammalian target of rapamycin (mTOR), in DC development, but whether and how Tsc1 directly regulate mature DC function in vivo remains elusive. Here we show that selective disruption of Tsc1 in DCs results in a lymphoproliferative disorder with the spontaneous activation of T cells. Tsc1 deficiency results in the activation of mTORC1-PPARγ pathway, which leads to the upregulation of neuropilin-1 (Nrp1) expression on DCs to stimulate naive T-cell proliferation...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28062852/a-proteomic-approach-to-identify-endosomal-cargoes-controlling-cancer-invasiveness
#18
Jesica Diaz-Vera, Sarah Palmer, Juan Ramon Hernandez-Fernaud, Emmanuel Dornier, Louise E Mitchell, Iain Macpherson, Joanne Edwards, Sara Zanivan, Jim C Norman
We have previously shown that Rab17, a small GTPase associated with epithelial polarity, is specifically suppressed by ERK2 (also known as MAPK1) signalling to promote an invasive phenotype. However, the mechanisms through which Rab17 loss permits invasiveness, and the endosomal cargoes that are responsible for mediating this, are unknown. Using quantitative mass spectrometry-based proteomics, we have found that knockdown of Rab17 leads to a highly selective reduction in the cellular levels of a v-SNARE (Vamp8)...
February 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28025892/tandem-peptide-based-on-structural-modification-of-poly-arginine-for-enhancing-tumor-targeting-efficiency-and-therapeutic-effect
#19
Yayuan Liu, Zhengze Lu, Ling Mei, Qianwen Yu, Xiaowei Tai, Yang Wang, Kairong Shi, Zhirong Zhang, Qin He
The nonselectivity of cell penetrating peptides had greatly limited the application in systemic administration. By conjugating a dGR motif to the C-terminal of octa-arginine, the formed tandem peptide R8-dGR had been proved to specifically recognize both integrin αvβ3 and neuropilin-1 receptors. However, the positive charge of poly-arginine would still inevitably lead to rapid clearance in the circulation system. Therefore, in this study, we tried to reduce the positive charge of poly-arginine by decreasing the number of arginine, to thus achieve improved tumor targeting efficiency...
January 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28000859/131i-labeled-monoclonal-antibody-targeting-neuropilin-receptor-type-2-for-tumor-spect-imaging
#20
Lichun Chen, Liangliang Wang, Jianghua Yan, Chao Ma, Jing Lu, Guoqiang Chen, Shengyou Chen, Fu Su, Weixing Wang, Xinhui Su
As a co-receptor for vascular endothelial growth factor‑3 (VEGF‑3), neuropilin receptor type‑2 (NRP‑2) plays a central role in lymphangiogenesis and angiogenesis. Recently, mounting data of evidence show that NRP‑2 is overexpressed in several human cancers, and its overexpression is often associated with poor prognosis. Therefore, it is necessary for us to develop an affinity reagent for noninvasive imaging of NRP‑2 expression because it may be possible to provide early cancer diagnosis, more accurate prognosis, and better treatment planning...
February 2017: International Journal of Oncology
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