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https://www.readbyqxmd.com/read/28444921/biochemical-characterization-and-analyses-of-polysialic-acid-associated-carrier-proteins-and-genes-in-piglets-during-neonatal-development
#1
Bing Wang, Yue Chen, He Ren, Nai Zhang, Frederic Arthur Troy Ii
Polysialic acid plays a key role in cancer metastasis and neurodevelopment. Our aim was to determine the developmental gene expression profiles for the two polysialyltransferases ST 8Sia II and ST8Sia IV, NCAM, SynCAM1, Neuropilin-2 (NRP2) and their polysialylated cognate glycans in different regions of the piglet brain during postnatal development. Our findings show that: (1) The cellular levels of mRNA coding for ST8Sia II and ST8Sia IV, NCAM, SynCAM1, NRP2 and polySia are age-dependent and cell type specific during neonatal brain development; (2) There was a lack of correlation between abundance level of mRNA coding for ST8Sia II and ST8Sia IV and the abundance level of the post-translation expression of polySia in all nine brain regions; (3) Expression levels of polySia did not correlate with the levels of the carrier proteins, NCAM-140, SynCAM1 and NRP2 in nine brain regions; (4) The cellular abundance of ST8Sia II and ST8Sia IV in nine subregions of piglet brain is regulated at the level of translation/posttranslation, and not at the level of transcription...
April 26, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28432397/downregulation-of-neuropilin-1-on-macrophages-modulates-antibody-mediated-tumoricidal-activity
#2
Kosuke Kawaguchi, Eiji Suzuki, Mariko Nishie, Isao Kii, Tatsuki R Kataoka, Masahiro Hirata, Masashi Inoue, Fengling Pu, Keiko Iwaisako, Moe Tsuda, Ayane Yamaguchi, Hironori Haga, Masatoshi Hagiwara, Masakazu Toi
Neuropilin-1 (NRP-1)-expressing macrophages are engaged in antitumor immune functions via various mechanisms. In this study, we investigated the role of NRP-1 on macrophages in antibody-mediated tumoricidal activity. Treatment of macrophages with NRP-1 knockdown or an anti-NRP-1-neutralizing antibody significantly suppressed antibody-dependent cellular cytotoxicity and modulated cytokine secretion from macrophages in vitro. Furthermore, in vivo studies using a humanized mouse model bearing human epidermal growth factor receptor-2 (HER2)-positive breast cancer xenografts showed that antibody-mediated antitumor activity and tumor infiltration of CD4(+) T lymphocytes were significantly downregulated when peripheral blood mononuclear cells in which NRP-1 was knocked down were co-administered with an anti-HER2 antibody...
April 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28418877/transforming-growth-factor-%C3%AE-1-promotes-breast-cancer-metastasis-by-downregulating-mir-196a-3p-expression
#3
Yan Chen, Shai Huang, Bo Wu, Jiankai Fang, Minsheng Zhu, Li Sun, Lifeng Zhang, Yongsheng Zhang, Maomin Sun, Lingling Guo, Shouli Wang
Transforming growth factor-β1 is considered a key contributor to the progression of breast cancer. MicroRNAs are important factors in the development and progression of many malignancies. In the present study, upon studies of breast cancer cell lines and tissues, we showed that microRNA -196a-3p is decreased by transforming growth factor-β1 in breast cancer cells and associated with breast cancer progression. We identified neuropilin-2 as a target gene of microRNA -196a-3p and showed that it is regulated by transforming growth factor-β1...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414297/tumor-penetrating-peptide-enhances-transcytosis-of-silicasome-based-chemotherapy-for-pancreatic-cancer
#4
Xiangsheng Liu, Paulina Lin, Ian Perrett, Joshua Lin, Yu-Pei Liao, Chong Hyun Chang, Jinhong Jiang, Nanping Wu, Timothy Donahue, Zev Wainberg, Andre E Nel, Huan Meng
Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal; however, some improvement in overall survival has been achieved with the introduction of nanocarriers that deliver irinotecan or paclitaxel. Although it is generally assumed that nanocarriers rely principally on abnormal leaky vasculature for tumor access, a transcytosis transport pathway that is regulated by neuropilin-1 (NRP-1) has recently been reported. NRP-1-mediated transport can be triggered by the cyclic tumor-penetrating peptide iRGD...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28407732/transcriptome-profiling-reveals-expression-signatures-of-cranial-neural-crest-cells-arising-from-different-axial-levels
#5
Rachael Lumb, Sam Buckberry, Genevieve Secker, David Lawrence, Quenten Schwarz
BACKGROUND: Cranial neural crest cells (NCCs) are a unique embryonic cell type which give rise to a diverse array of derivatives extending from neurons and glia through to bone and cartilage. Depending on their point of origin along the antero-posterior axis cranial NCCs are rapidly sorted into distinct migratory streams that give rise to axial specific structures. These migratory streams mirror the underlying segmentation of the brain with NCCs exiting the diencephalon and midbrain following distinct paths compared to those exiting the hindbrain rhombomeres (r)...
April 13, 2017: BMC Developmental Biology
https://www.readbyqxmd.com/read/28397127/a-novel-strategy-to-enhance-angiogenesis-in-vivo-using-the-small-vegf-binding-peptide-pr1p
#6
Avner Adini, Irit Adini, Zai-Long Chi, Ratmir Derda, Amy E Birsner, Benjamin D Matthews, Robert J D'Amato
Therapeutic angiogenesis is an experimental frontier in vascular biology that seeks to deliver angiogenic growth factors to ischemic or injured tissues to promote targeted formation of new blood vessels as an alternative approach to surgical revascularization procedures. Vascular endothelial growth factor (VEGF) is a potent angiogenic signal protein that is locally upregulated at sites of tissue injury. However, therapies aimed at increasing VEGF levels experimentally by injecting VEGF gene or protein failed to improve outcomes in human trials in part due to its short half-life and systemic toxicity...
April 10, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28360225/biomarker-profiles-in-heart-failure-patients-with-preserved-and-reduced-ejection-fraction
#7
Jasper Tromp, Mohsin A F Khan, IJsbrand T Klip, Sven Meyer, Rudolf A de Boer, Tiny Jaarsma, Hans Hillege, Dirk J van Veldhuisen, Peter van der Meer, Adriaan A Voors
BACKGROUND: Biomarkers may help us to unravel differences in the underlying pathophysiology between heart failure (HF) patients with a reduced ejection fraction (HFrEF) and a preserved ejection fraction (HFpEF). Therefore, we compared biomarker profiles to characterize pathophysiological differences between patients with HFrEF and HFpEF. METHODS AND RESULTS: We retrospectively analyzed 33 biomarkers from different pathophysiological domains (inflammation, oxidative stress, remodeling, cardiac stretch, angiogenesis, arteriosclerosis, and renal function) in 460 HF patients (21% HFpEF, left ventricular ejection fraction ≥45%) measured at discharge after hospitalization for acute HF...
March 30, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28358432/irgd-as-a-tumor%C3%A2-penetrating-peptide-for-cancer-therapy-review
#8
Hong Yin, Jie Yang, Qing Zhang, Jie Yang, Haiyu Wang, Jinjing Xu, Junnian Zheng
As a tumor-targeting and ‑penetrating peptide, iRGD binds to αv integrins and neuropilin‑1 receptors, which are expressed at high levels on tumor cells and the surfaces of vasculature. Subsequently, iRGD penetrates deep into the tumor parenchyma with antitumor drugs, imaging agents, immune modulators and biological products. These substances are either chemically linked to the peptide or co‑injected with the peptide. The iRGD peptide can be readily synthesized, exhibits significantly improved penetration, compared with traditional peptides, and can effectively inhibit tumor metastasis...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338957/regulation-of-tgf-%C3%AE-mediated-endothelial-mesenchymal-transition-by-microrna-27
#9
Hiroshi I Suzuki, Akihiro Katsura, Hajime Mihira, Masafumi Horie, Akira Saito, Kohei Miyazono
Multiple microRNAs (miRNAs) regulate epithelial-mesenchymal transition and endothelial-mesenchymal transition (EndMT). Here we report that microRNA-27b (miR-27b) positively regulates transforming growth factor-β (TGF-β)-induced EndMT of MS-1 mouse pancreatic microvascular endothelial cells. TGF-β induced miR-23b/24-1/27b expression, and inhibition of miR-27 suppressed TGF-β-mediated induction of mesenchymal genes. Genome-wide miRNA target analysis revealed that miR-27 targets Elk1, which acts as a competitive inhibitor of myocardin-related transcription factor-serum response factor signalling and as a myogenic repressor...
March 13, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28325756/a-novel-role-for-myeloid-cell-specific-neuropilin-1-in-mitigating-sepsis
#10
Xiaoyan Dai, Imoh Okon, Zhaoyu Liu, Yue Wu, Huaiping Zhu, Ping Song, Ming-Hui Zou
Sepsis-typically caused by an uncontrolled and amplified host systemic inflammatory response to microbial infection-is a life-threatening complex clinical disorder and remains a major cause of infection-related deaths in the intensive care unit. Emerging evidence suggests that neuropilin 1 (Nrp1), an originally defined coreceptor for class 3 semaphorins and VEGF, plays important roles in the immune system; however, the function and regulation of macrophage Nrp1 in host immune defense against bacterial infection remain unknown...
March 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28319199/a-computational-analysis-of-in-vivo-vegfr-activation-by-multiple-co-expressed-ligands
#11
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 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
#12
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
#13
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
#14
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...
April 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
#15
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
#16
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-pdgf-d-and-is-a-co-receptor-in-pdgf-d-pdgfr%C3%AE-signaling
#17
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 neuropilin 1 (NRP1), in a manner that requires the PDGF-D C-terminal Arg residue. 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, independently of PDGFRβ, altering the availability of NRP1 for VEGF-A-VEGFR2 signaling...
April 15, 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
#18
Masayuki Yamane, Naoya Yamashita, Tomonobu Hida, Yoshinori Kamiya, Fumio Nakamura, Pappachan Kolattukudy, Yoshio Goshima
Semaphorin3A (Sema3A) is a secreted type of axon guidance molecule that regulates axon wiring through complexes of neuropilin-1 (NRP1) with PlexinA protein receptors. Sema3A regulates the dendritic branching through tetrodotoxin (TTX)-sensitive retrograde axonal transport of PlexA proteins and tropomyosin-related kinase A (TrkA) complex. We here demonstrate that Nav1.7 (encoded by SCN9A), a TTX-sensitive Na(+) channel, by coupling with collapsin response mediator protein 1 (CRMP1), mediates the Sema3A-induced retrograde transport...
April 15, 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
#19
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
#20
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
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