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You-Jung Ha, Dong Woo Han, Ji Hyoun Kim, Sang Wan Chung, Eun Ha Kang, Yeong Wook Song, Yun Jong Lee
Semaphorin 3A (Sema3A) and semaphorin 4D (Sema4D) are molecules which regulate immune responses as well as bone remodeling process. The aim of this study was to evaluate the serum levels of Sema3A and Sema4D and to investigate their clinical significance in rheumatoid arthritis (RA). The serum levels of Sema3A and Sema4D were measured in 130 patients with RA and 65 sex- and age-matched healthy individuals. Circulating levels of biomarkers of RA-related inflammation and bone turnover such as tumor necrosis factor- (TNF-) α , interleukin- (IL-) 6, IL-22, IL-34, osteopontin, Dkk-1, and sclerostin were also measured...
2018: Disease Markers
Jung-Hyun Choi, Sung-Hoon Kim, Young-Hun Jeong, Sung Wook Kim, Kyung-Tai Min, Kyong-Tai Kim
Fragile X syndrome (FXS) caused by loss of fragile X mental retardation protein (FMRP) is the most common cause of inherited intellectual disability. Numerous studies show that FMRP is a RNA binding protein that regulates translation of its binding targets and plays key roles in neuronal functions. However, the regulatory mechanism for FMRP expression is incompletely understood. Conflicting results regarding internal ribosome entry site (IRES)-mediated fmr1 translation were reported. Here, we unambiguously demonstrated that the fmr1 gene, which encodes FMRP, exploits both IRES-mediated translation and canonical cap-dependent translation...
November 26, 2018: Molecular and Cellular Biology
Chun-Wai Ma, Pui-Yi Kwan, Kenneth Lap-Kei Wu, Daisy Kwok-Yan Shum, Ying-Shing Chan
Perineuronal nets (PN) restrict neuronal plasticity in the adult brain. We hypothesize that activity-dependent consolidation of PN is required for functional maturation of behavioral circuits. Using the postnatal maturation of brainstem vestibular nucleus (VN) circuits as a model system, we report a neonatal period in which consolidation of central vestibular circuitry for graviception is accompanied by activity-dependent consolidation of chondroitin sulfate (CS)-rich PN around GABAergic neurons in the VN. Postnatal onset of negative geotaxis was used as an indicator for functional maturation of vestibular circuits...
November 20, 2018: Brain Structure & Function
M Ribeiro-da-Silva, D M Vasconcelos, I S Alencastre, M J Oliveira, D Linhares, N Neves, G Costa, R Henrique, M Lamghari, C J Alves
Inflammation is a common symptom in joint disorders such as rheumatoid arthritis, osteoarthritis (OA) and implant aseptic loosening (AL). The sympathetic nervous system is well known to play a critical role in regulating inflammatory conditions, and imbalanced sympathetic activity has been observed in rheumatoid arthritis. In AL it is not clear whether the sympathetic nervous system is altered. In this study we evaluated the systemic and local profile of neuroimmune molecules involved in the interplay between the sympathetic nervous system and the periprosthetic inflammation in hip AL...
October 30, 2018: Scientific Reports
Guang Wang, Ling-Min Jiang, Bao-Yi Tan, Pei-Zhi Li, Pei-Ling Zhang, Yu Zhang, Xin Cheng, Zheng-Lai Ma, Zhi-Jie Li, Beate Brand-Saberi, Xuesong Yang
In this study, we investigated the effect of caffeine overexposure on corneal innervation in the early chicken embryo. Caffeine administration restricted corneal innervation by affecting trigeminal nerve development. Immunohistochemistry for phospho-Histone3 (pHIS3) and C-caspase3 revealed that cell survival was repressed by caffeine administration. Whole-mount in situ hybridization against semaphorin 3A (Sema3A) and neuropilin-1 (Nrp1) showed that both caffeine and 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH, a free radical generator) administration upregulates the expression of both Sema3A and Nrp1...
October 26, 2018: Journal of Cellular Physiology
Kenichiro Hira, Yuji Ueno, Ryota Tanaka, Nobukazu Miyamoto, Kazuo Yamashiro, Toshiki Inaba, Takao Urabe, Hideyuki Okano, Nobutaka Hattori
Background and Purpose- Exosomes play a pivotal role in neurogenesis. In the peri-infarct area after stroke, axons begin to regenerate but are inhibited by astrocyte scar formation. The direct effect and underlying molecular mechanisms of astrocyte-derived exosomes on axonal outgrowth after ischemia are not known. Methods- Using a semaphorin 3A (Sema3A) inhibitor, we explored neuronal signaling during axonal outgrowth after ischemia in rats subjected to middle cerebral artery occlusion and in cultured cortical neurons challenged with oxygen-glucose deprivation...
October 2018: Stroke; a Journal of Cerebral Circulation
Nannan Wang, Pratibha Dhumale, Joanna Chiang, Andreas W Püschel
The highly conserved Rap1 GTPases perform essential functions during neuronal development. They are required for the polarity of neuronal progenitors and neurons as well as for neuronal migration in the embryonic brain. Neuronal polarization and axon formation depend on the precise temporal and spatial regulation of Rap1 activity by guanine nucleotide exchange factors (GEFs) and GTPases-activating proteins (GAPs). Several Rap1 GEFs have been identified that direct the formation of axons during cortical and hippocampal development in vivo and in cultured neurons...
October 23, 2018: Scientific Reports
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
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