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Noa Lavi, Ofra Kessler, Keren Ziv, Inbal Nir-Zvi, Yelena Mumblat, Nasrene Eiza, Yael Paran, Benjamin Brenner, Zahava Vadasz, Gera Neufeld
Previous studies revealed that progression of multiple myeloma (MM) is associated with down regulation of semaphorin-3A (sema3A) expression in bone marrow endothelial cells. We therefore determined if serum sema3A concentrations are correlated with MM progression and if sema3A can affect MM progression. We find that the concentration of sema3A in sera of MM patients is strongly reduced and that the decrease is correlated with disease progression. A similar depletion is found in AML and ALL leukemia patients but not in cancer forms that do not involve the bone marrow such as in colon cancer...
August 9, 2018: Carcinogenesis
Hua-Zhi Wen, Ping Xie, Fu Zhang, Yu Ma, Yan-Ling Li, Sheng-Kai Xu
BACKGROUND: Electrical remodeling at infarct border zone (IBZ) has been shown to contribute to the occurrence of ventricular arrhythmias after myocardial infarction (MI). Sema3A has been demonstrated to reduce the inducibility of ventricular arrhythmias. Neuropilin 1 (NRP1) is the receptor of Sema3A. In the present study, we investigated whether treatment with NRP1 can ameliorate electrical remodeling at IBZ after MI. METHODS AND RESULTS: Wistar rats underwent sham operation (n = 20), the ligation of left coronary artery (MI group, n = 30), MI with control adenovirus (Ad group, n = 30), and MI with NRP1 adenovirus (NRP1 group, n = 30)...
August 9, 2018: Autonomic Neuroscience: Basic & Clinical
Shuang Hao, Xiaokang Liu, Xin Sui, Yu Pei, Zhenxing Liang, Nan Zhou
OBJECTIVE: To investigate the role of GAS5 on cardiomyocyte apoptosis. METHODS: Myocardial infarction (MI) model was established by the left-anterior descending coronary artery ligation. Norepinephrine (NE) was used to induce cardiomyocyte apoptosis. GAS5 levels and mRNA expressions of Semaphorin 3a (sema3a) were measured by qRT-PCR. Protein level of sema3a was detected by Western blotting. Cardiomyocyte apoptosis was detected by flow cytometry assay. RNA pull-down and RIP assay were used to verify the combination between GAS5 and sema3a...
August 9, 2018: International Journal of Biological Macromolecules
Chenfei Wang, Yihua Song, Zhifeng Gu, Min Lian, Dan Huang, Xiaohui Lu, Xingmei Feng, Qi Lu
Wedelolactone is a multitarget natural plant compound with many pharmacological activities, including anti-inflammatory, anticancer, and antiosteoporosis. In this study, dental pulp stem cells (DPSCs) were treated with or without wedelolactone. We found that wedelolactone stimulated odontoblast differentiation and mineralization. At the molecular level, wedelolactone directly promoted the nuclear accumulation of β-catenin, and thereafter stimulated the expression of odontoblast-related marker genes containing dentin matrix protein-1 (DMP1), dentin sialophosphoprotein (DSPP), and runt-related transcription factor 2 (Runx2)...
August 2018: Cellular Reprogramming
Ya He, Ying Yang, Ruili Wang, Hui Wang, Qiaoya Ma, Songsheng Chen, Daiying Shi
To investigate the expression changes and roles of Semaphorin3A (Sema3A) and Neuropilin-1 (Nrp1) in cultured rat cortical neurons after oxygen glucose deprivation (OGD). Cultured cortical neurons of newborn SD rats were divided randomly into control group and OGD treatment group. Western blot was performed to detect the expression of Sema3A and Nrp-1 protein and TUNEL was used to detect apoptosis. With the increase of OGD treatment time, the cells become swollen, the axon disintegrated and death cells increased...
June 30, 2018: Cellular and Molecular Biology
Roberta Cagnetta, Christian K Frese, Toshiaki Shigeoka, Jeroen Krijgsveld, Christine E Holt
Axonal protein synthesis and degradation are rapidly regulated by extrinsic signals during neural wiring, but the full landscape of proteomic changes remains unknown due to limitations in axon sampling and sensitivity. By combining pulsed stable isotope labeling of amino acids in cell culture with single-pot solid-phase-enhanced sample preparation, we characterized the nascent proteome of isolated retinal axons on an unparalleled rapid timescale (5 min). Our analysis detects 350 basally translated axonal proteins on average, including several linked to neurological disease...
July 11, 2018: Neuron
Frédéric Charron
In this issue of Neuron, Cagnetta et al. (2018) describe a novel method to identify, in an unbiased manner, newly synthesized axonal proteins in response to axon guidance cues. They find that axons stimulated by different guidance cues (Netrin-1, BDNF, and Sema3A) show distinct and common signatures.
July 11, 2018: Neuron
Bo Huang, Qin Zhang, Ying Yuan, Na Xin, Kun He, Yan Huang, Hua Tang, Ping Gong
Astronauts and cancer patients receive different types of radiation, and radiation decreases bone strength and leads to radiation-induced osteoporosis. This effect is attributed to the activation of osteoclasts. Our aim was to study the effect of Sema3a on the differentiation of the murine macrophage cell line Raw264.7 into osteoclasts upon irradiation. Raw264.7 cells were divided into four groups: A, receiving no radiation; B, receiving no radiation + 50ngng/ml Sema3a; C, receiving 2Gy radiation; and D, receiving 2Gy radiation +50ngng/ml Sema3a...
2018: PloS One
Q Qiao, Y L Song, F L Li
Objective: To evaluate the effect of semaphorin 3A (Sema3A) pre-treated bone marrow mesenchymal stem cells (BMSC) sheets on new bone formation in type 2 diabetes mellitus rats. Methods: Type 2 diabetes mellitus (T2DM) were induced by injection of streptozotocin, and the BMSC were isolated, controlled, identified and induced into cell sheets. Fifteen T2DM rats were randomly divided into control, sheets and Sema3A-sheets group and the calvarial critical size defect (CSD) model of rats were established. The defect zone of rats from control group were implanted with bone powder...
May 9, 2018: Zhonghua Kou Qiang Yi Xue za Zhi, Zhonghua Kouqiang Yixue Zazhi, Chinese Journal of Stomatology
Marina Kiso, Sunao Tanaka, Shigehira Saji, Masakazu Toi, Fumiaki Sato
VEGF stimulates endothelial cells as a key molecule in angiogenesis. VEGF also works as a multi-function molecule, which targets a variety of cell members in the tumor microenvironment. We aimed to reveal VEGF-related molecular mechanisms on breast cancer cells. VEGF-knocked-out MDA-MB-231 cells (231VEGFKOex3 ) showed rounded morphology and shorter perimeter (1.6-fold, P<0.0001). 231VEGFKOex3 cells also showed impaired cell migration (2.6-fold, P=0.002). Bevacizumab treatment did not induce any change in morphology and mobility...
July 4, 2018: International Journal of Cancer. Journal International du Cancer
Ying Wang, Xiaomei Bao, Shiyang Wu, Xiya Shen, Fan Zhang, Zhaoting Lv, Qian Wu, Changnan Xie, Huitao Liu, Jian Lin, Honglin Teng, Zhihui Huang
Olfactory ensheathing cells (OECs) migrate from olfactory epithelium towards olfactory bulb (OB), contributing to formation of the presumptive olfactory nerve layer during development. However, it remains unclear that molecular mechanism of regulation of OEC migration in OB. In the present study, we found that OECs highly expressed the receptors of semaphorin 3A (Sema3A) in vitro and in vivo, whereas Sema3A displayed a gradient expression pattern with higher in inner layer of OB and lower in outer layer of OB...
June 27, 2018: Molecular and Cellular Neurosciences
Xiaofang Tian, Hua Gan, Yizhou Zeng, Hongfei Zhao, Rong Tang, Yunfeng Xia
Semaphorin-3a (Sema3A), a soluble axon guidance cue, appears to play an important role in the development of acute kidney injury (AKI) and has been regarded as an early diagnostic marker to evaluate the progression of AKI. However, the role of Sema3A in sepsis-associated AKI remains unknown. In this study, lipopolysaccharide (LPS) was used to simulate sepsis-associated AKI and the role of Sema3A in LPS-induced AKI was investigated in vivo and in vitro. In our in vivo study, Sema3A was found in tubular epithelial cells (TECs), which presented a higher level after LPS treatment...
June 16, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Joseph R Podojil, Ming-Yi Chiang, Igal Ifergan, Ronald Copeland, Linda N Liu, Sebastien Maloveste, Solomon Langermann, David Liebenson, Roumen Balabanov, Hongbo Chi, Lieping Chen, Dario A A Vignali, Stephen D Miller
The potent immune regulatory function of an agonistic B7-H4-Ig fusion protein (B7-H4Ig) has been demonstrated in multiple experimental autoimmune models; however, the identity of a functional B7-H4 receptor remained unknown. The biological activity of B7-H4 is associated with decreased inflammatory CD4+ T cell responses as supported by a correlation between B7-H4-expressing tumor-associated macrophages and Foxp3+ T cells within the tumor microenvironment. Recent data indicate that members of the semaphorin (Sema)/plexin/neuropilin (Nrp) family of proteins both positively and negatively modulate immune cell function...
August 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
K Yang, R J Miron, Z Bian, Y F Zhang
Osteoporosis is a serious health problem worldwide. Semaphorins (Sema) have been described as key molecules involved in the cross-talk between bone cells (osteoblasts/osteoclasts). In this study, we investigated whether plasmid containing Sema3a could ameliorate bone loss in an ovariectomized (OVX) mouse model via (AspSerSer)6 , a selectively bone-targeting moiety. Plasmid pcDNA3.1(+)-Sema3a-GFP was fabricated and transfected cells with the plasmid demonstrated statistically higher levels of Sema3A in vitro (p < 0...
September 2018: Bone
Chikako Sumi, Naoto Hirose, Makoto Yanoshita, Mami Takano, Sayuri Nishiyama, Yuki Okamoto, Yuki Asakawa, Kotaro Tanimoto
Background: Excessive mechanical stress causes inflammation and destruction of cartilage and is considered one of the cause of osteoarthritis (OA). Expression of semaphorin 3A (Sema3A), which is an axon guidance molecule, has been confirmed in chondrocytes. However, there are few reports about Sema3A in chondrocytes, and the effects of Sema3A on inflammation in the cartilage are poorly understood. The aim of this study was to examine the role of Sema3A in inflammation caused by high magnitude cyclic tensile strain (CTS)...
2018: Mediators of Inflammation
Yujiao Han, Xiuling You, Wenhui Xing, Zhong Zhang, Weiguo Zou
The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes, and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenesis in a paracrine manner. Osteoblasts secrete a range of different molecules including RANKL/OPG, M-CSF, SEMA3A, WNT5A, and WNT16 that regulate osteoclastogenesis. Osteoblasts also produce VEGFA that stimulates osteoblastogenesis and angiogenesis. Osteocytes produce sclerostin (SOST) that inhibits osteoblast differentiation and promotes osteoclast differentiation...
2018: Bone Research
Noemi Gioelli, Federica Maione, Chiara Camillo, Michela Ghitti, Donatella Valdembri, Noemi Morello, Marie Darche, Lorena Zentilin, Gabriella Cagnoni, Yaqi Qiu, Mauro Giacca, Maurizio Giustetto, Michel Paques, Ilaria Cascone, Giovanna Musco, Luca Tamagnone, Enrico Giraudo, Guido Serini
Vascular normalizing strategies, aimed at ameliorating blood vessel perfusion and lessening tissue hypoxia, are treatments that may improve the outcome of cancer patients. Secreted class 3 semaphorins (SEMA3), which are thought to directly bind neuropilin (NRP) co-receptors that, in turn, associate with and elicit plexin (PLXN) receptor signaling, are effective normalizing agents of the cancer vasculature. Yet, SEMA3A was also reported to trigger adverse side effects via NRP1. We rationally designed and generated a safe, parenterally deliverable, and NRP1-independent SEMA3A point mutant isoform that, unlike its wild-type counterpart, binds PLXNA4 with nanomolar affinity and has much greater biochemical and biological activities in cultured endothelial cells...
May 23, 2018: Science Translational Medicine
Qiao Qiao, Xiaoru Xu, Yingliang Song, Shuang Song, Wenzhong Zhu, Fenglan Li
Bone regeneration is impaired in patients with type 2 diabetes mellitus (T2DM), which leads to non-healing after bone loss. The decreased osteogenic capacity of bone mesenchymal stem cells (BMSCs) might be a main reason. Sema3A, as a powerful protein promoting osteocyte differentiation, shows potential for bone regeneration treatment. BMSCs may be a therapeutic solution. In this study, we divided BMSCs from T2DM rats (BMSCs-D) and normal rats (BMSCs-N), identified their ability to differentiate into different cell types...
August 2018: Journal of Molecular Histology
Jennifer L Shadrach, Brian A Pierchala
The neuromuscular junction (NMJ) is a specialized synapse that is formed by motor axon innervation of skeletal muscle fibers. The maintenance of motor-muscle connectivity is critical for the preservation of muscle tone and generation of movement. Injury can induce a robust regenerative response in motor axons, but severe trauma or chronic denervation resulting from neurodegenerative disease typically leads to inefficient repair and poor functional recovery. The axon guidance molecule Semaphorin3A (Sema3A) has been implicated as a negative regulator of motor innervation...
May 2018: ENeuro
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