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I Valiulyte, V Preitakaite, A Tamasauskas, A Kazlauskas
Angiogenesis is one of the key processes in the growth and development of tumors. Class-3 semaphorins (Sema3) are characterized as axon guidance factors involved in tumor angiogenesis by interacting with the vascular endothelial growth factor signaling pathway. Sema3 proteins convey their regulatory signals by binding to neuropilins and plexins receptors, which are located on the effector cell. These processes are regulated by furin endoproteinases that cleave RXRR motifs within the Sema, plexin-semaphorins-integrin, and C-terminal basic domains of Sema3 protein...
October 8, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Takashi S Kajii, Akira Oka, Mitsutoki Hatta, Jun Yamazaki, Junro Yamashita, Junichiro Iida
In a previous genome-wide association study, plexin A2 ( PLXNA2 ) was suggested as one of the candidate genes for mandibular prognathism. PLXNA2 encodes plexin A2, a member of the plexin-A family of semaphorin co-receptors. Semaphorin 3A (sema3A) exerts an osteoprotective effect. However, to the best of our knowledge, there have been no previous studies examining the role of sema3A or plexin A2 on human chondrocytes. The objectives of the present study were to examine the function of sema3A and its receptor, plexin A2, in human chondrocytes...
September 2018: Biomedical Reports
XiaoKang Liu, Nan Zhou, Xin Sui, Yu Pei, ZhenXing Liang, Shuang Hao
OBJECTIVE: To explore the underlying mechanisms of Hrd1/sema3a/IGF-1R on cardiomyocyte apoptosis. METHODS: AMI model was established by the left-anterior descending coronary artery (LAD) ligation. The expressions of Hrd1, sema3a and IGF-1R were examined by western blot. The activity of caspase-3 and caspase-8 was measured using the corresponding activity detection kit. Cardiomyocyte apoptosis was detected by flow cytometry assay. Co-immunoprecipitation and ubiquitination assay were used to test the relationship among Hrd1, sema3a and IGF-1R...
September 21, 2018: Biochimica et biophysica acta. Molecular basis of disease
Jörg Hänze, Peter Rexin, Peter Jakubowski, Henner Schreiber, Hendrik Heers, Susanne Lingelbach, Ralf Kinscherf, Eberhard Weihe, Rainer Hofmann, Axel Hegele
Innervation of prostate cancer (CaP) tissue favors tumor progression and metastasis but the regulation of innervation in CaP is unclear. The oncogenic transcription factor ERG is commonly induced by a typical TMPRSS2-ERG (TE) gene fusion in CaP and may affect innervation. Here, we analyzed whether nerve density of CaP tissue is related to TE status or perineural infiltration status of CaP tissue. In parallel, we measured several members of the neuropilin/plexin/semaphorin family (NRP, PLXN, and SEMA) as possible targets mediating innervation...
September 18, 2018: Urologic Oncology
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)...
November 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...
December 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
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