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Fabio Massimo Perrotta, Fulvia Ceccarelli, Cristiana Barbati, Tania Colasanti, Monica Montepaone, Cristiano Alessandri, Guido Valesini, Ennio Lubrano
OBJECTIVES: Several molecules are involved in the pathogenesis of new bone formation in ankylosing spondylitis (AS). The aim of the present study was to evaluate serum levels of semaphoring 3A in AS and to investigate any correlations with radiographic damage, disease activity, function and treatment. METHODS: AS patients who fulfilled the modified New York criteria were enrolled for this study. Healthy subjects were also enrolled as control group. BASDAI, ASDAS-CRP, BASMI, BASFI, patients and physician VAS, C-reactive protein and erythrocyte sedimentation rate were evaluated at baseline visit...
October 26, 2016: Clinical and Experimental Rheumatology
Roberta Schellino, Sara Trova, Irene Cimino, Alice Farinetti, Bart C Jongbloets, R Jeroen Pasterkamp, Giancarlo Panzica, Paolo Giacobini, Silvia De Marchis, Paolo Peretto
Opposite-sex attraction in most mammals depends on the fine-tuned integration of pheromonal stimuli with gonadal hormones in the brain circuits underlying sexual behaviour. Neural activity in these circuits is regulated by sensory processing in the accessory olfactory bulb (AOB), the first central station of the vomeronasal system. Recent evidence indicates adult neurogenesis in the AOB is involved in sex behaviour; however, the mechanisms underlying this function are unknown. By using Semaphorin 7A knockout (Sema7A ko) mice, which show a reduced number of gonadotropin-releasing-hormone neurons, small testicles and subfertility, and wild-type males castrated during adulthood, we demonstrate that the level of circulating testosterone regulates the sex-specific control of AOB neurogenesis and the vomeronasal system activation, which influences opposite-sex cue preference/attraction in mice...
October 26, 2016: Scientific Reports
Patrick Mucka, Nicholas Levonyak, Elena Geretti, Bernadette M M Zwaans, Xiaoran Li, Irit Adini, Michael Klagsbrun, Rosalyn M Adam, Diane R Bielenberg
The vasculature influences the progression and resolution of tissue inflammation. Capillaries express vascular endothelial growth factor (VEGF) receptors, including neuropilins (NRPs), which regulate interstitial fluid flow. NRP2, a receptor of VEGFA and semaphorin (SEMA) 3F ligands, is expressed in the vascular and lymphatic endothelia. Previous studies have demonstrated that blocking VEGF receptor 2 attenuates VEGFA-induced vascular permeability. The inhibition of NRP2 was hypothesized to decrease vascular permeability as well...
October 12, 2016: American Journal of Pathology
Michael Rehman, Sreeharsha Gurrapu, Gabriella Cagnoni, Lorena Capparuccia, Luca Tamagnone
The secreted semaphorin Sema3E controls cell migration and invasiveness in cancer cells. Sema3E-receptor, PlexinD1, is frequently upregulated in melanoma, breast, colon, ovarian and prostate cancers; however, the mechanisms underlying PlexinD1 upregulation and the downstream events elicited in tumor cells are still unclear. Here we show that the canonical RBPjk-dependent Notch signaling cascade controls PlexinD1 expression in primary endothelial and cancer cells. Transcriptional activation was studied by quantitative PCR and promoter activity reporter assays...
2016: PloS One
Xiaodong Cai, Ling Long, Libai Yang, Ziyi Chen, Guanzhong Ni, Jiaming Qin, Jueqian Zhou, Liemin Zhou
OBJECTIVES: Mossy fiber sprouting is involved in the pathogenesis of mesial temporal lobe epilepsy. But the exact mechanism of formation of mossy fiber sprouting is still unclear. Semaphorin-3f protein could inhibit the growth of neuron axons. The aim of this research is to evaluate the association between semaphorin-3f expression and mossy fiber sprouting. METHODS: We established pilocarpine-induced status epilepticus (PISE) models firstly. Then, mossy fiber sprouting in the hippocampus of PISE models was examined by Timm staining...
October 17, 2016: Neurological Research
Daisuke Ito, Atsushi Kumanogoh
Semaphorins were originally identified as axon guidance cues that regulate the functional activity of axons in the nervous system. In addition, accumulating evidence indicates that semaphorins have multiple functions in physiological and pathogenic processes, including vascular development, tumor progression, and immune responses. Sema4A is a semaphorin expressed in immune cells, and is thus termed an "immune semaphorin." Sema4A has four types of receptors: Plexin D family, Plexin B family, Tim-2, and Nrp-1...
October 13, 2016: Cell Adhesion & Migration
G Wang, P-P Wang, P-P Meng, C Han, S-W Yue
OBJECTIVE: Cerebral ischemia-reperfusion is the major pathophysiological process in stroke and can cause severe and lasting sequel. However, an intensive exercise training can potentially effect a quick and efficient recovery. We used swimming training on rats with cerebral ischemia-reperfusion (CIR) and explore the underlying neuroprotective mechanism(s), including the effects of intensive training on the expression of semaphorin 3A (Sema3A) and its receptor Neuropilin-1 (NRP-1). MATERIALS AND METHODS: The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established by inserting a thread into the middle cerebral artery of Sprague-Dawley (SD) rats, and randomly dividing into the control group and training groups for different training intensities...
September 2016: European Review for Medical and Pharmacological Sciences
Hongchao Jiang, Ceshi Chen, Qiangming Sun, Jing Wu, Lijuan Qiu, Change Gao, Weiqing Liu, Jun Yang, Nie Jun, Jian Dong
BACKGROUND: Semaphorin 4D (Sema4D) is highly expressed in certain types of tumors and functions in the regulation of tumor angiogenesis and growth. However, it is still not clear regarding the roles of Sema4D in breast cancer. This study was designed to explore the effects of Sema4D on proliferation, cell cycle progression, apoptosis, invasion, migration, tumor growth, and angiogenesis in breast cancer. MATERIALS AND METHODS: The expression level of Sema4D was investigated in MCF10A, 184A1, HCC1937, MDA-MB-468, MDA-MB-231, Hs578T, BT474, MCF-7, and T47D breast cancer cell lines by Western blotting analysis...
2016: OncoTargets and Therapy
Shira Toledano, Huayi Lu, Agustina Palacio, Boaz Kigel, Ofra Kessler, Gilad Allon, Yoreh Barak, Gera Neufeld, Shlomit Schaal
Abnormal subretinal choroidal neovascularization (CNV) is a major cause of blindness in exudative age-related macular degeneration (AMD). Current anti-angiogenic treatments by VEGF sequestering agents have been successful, but a significant proportion of patients do not respond well to these treatments, and the response of others diminishes over time, suggesting that additional anti-angiogenic agents that function by separate mechanisms may be of use to such patients. We have previously found that a point mutated form of semaphorin-3E resistant to cleavage by furin like pro-protein convertases (UNCL-Sema3E) displays potent anti-angiogenic properties...
October 7, 2016: Experimental Eye Research
Fatemeh Sharifpanah, Sascha Behr, Maria Wartenberg, Heinrich Sauer
OBJECTIVES: Differentiation of embryonic stem (ES) cells may be regulated by mechanical strain. Herein, signaling molecules underlying mechanical stimulation of vasculogenesis and expression of angiogenesis guidance cues were investigated in ES cell-derived embryoid bodies. METHODS AND RESULTS: Treatment of embryoid bodies with 10% static mechanical strain using a Flexercell strain system significantly increased CD31-positive vascular structures and the angiogenesis guidance molecules plexinB1, ephrin B2, neuropilin1 (NRP1), semaphorin 4D (sem4D) and robo4 as well as vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor-BB (PDGF-BB) as evaluated by Western blot and real time RT-PCR...
October 8, 2016: Biochimica et Biophysica Acta
Xiangwei Liu, Naiwen Tan, Yuchao Zhou, Xueying Zhou, Hui Chen, Hongbo Wei, Ji Chen, Xiaoru Xu, Sijia Zhang, Guodong Yang, Yingliang Song
Adipose mesenchymal stem cells (ASCs) are considered as the promising seed cells for bone regeneration. However, the lower osteogenic differentiation capacity limits its therapeutic efficacy. Identification of the key molecules governing the differences between ASCs and BMSCs would shed light on manipulation of ASCs towards osteogenic phenotype. In this study, we screened semaphorin family members in ASCs and BMSCs and identified Sema3A as an osteogenic semaphorin that was significantly and predominantly expressed in BMSCs...
2016: Stem Cells International
Alexandru Movila, Hani Mawardi, Kazuaki Nishimura, Tomomi Kiyama, Kenji Egashira, Jae-Young Kim, Alessandro Villa, Hajime Sasaki, Sook-Bin Woo, Toshihisa Kawai
Prior consensus held that medication-related osteonecrosis of the jaw (MRONJ) lesion was composed of necrotic bone; however, more recent studies have identified inflammatory infiltrates in the lesion. Herein, we report that remarkably elevated infiltrating γδT cells (90% of lymphocytes) express Semaphorin 4D (Sema4D) in human patient with MRONJ lesion, whereas γδT cells only account for 2-5% of lymphocytes in blood. Importantly, Sema4D is implicated in the pathogenesis of T cell-mediated inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis...
October 5, 2016: Biochemical and Biophysical Research Communications
Daisuke Yamada, Satoshi Watanabe, Kohichi Kawahara, Takehiko Maeda
Aberrant changes to several signaling pathways because of genetic mutations or increased cytokine production are critical for tumor cells to become malignant. Semaphorin 3A (SEMA3A) acts as a bivalent factor that suppresses or promotes tumor development in different pathological backgrounds. Previously, we showed that SEMA3A positively regulated the proliferative and glycolytic activities of mouse-derived Lewis lung carcinoma (LLC) cells. Plexins A1-A4 (PLXNA1-PLXNA4) are SEMA3A receptors; however, it is not known which subtype is critical for oncogenic SEMA3A signaling...
October 4, 2016: Biochemical and Biophysical Research Communications
Keijo Luukko, Päivi Kettunen
The tooth, like many other organs, develops from both epithelial and mesenchymal tissues, and has proven to be a valuable tool with which to investigate organ formation and peripheral innervation. Tooth formation is regulated by local epithelial-mesenchymal tissue interactions, and is closely integrated with stereotypic dental nerve navigation and patterning. Recent analyses of the function and regulation of semaphorin 3A (SEMA3A) have shed light on the regulatory mechanisms that coordinate organogenesis and innervation at the tissue and molecular levels...
August 9, 2016: Cell Adhesion & Migration
Tomoyuki Masuda, Masahiko Taniguchi
Semaphorins are a large family of proteins characterized by sema domains and play a key role not only in the formation of neural circuits, but in the immune system, angiogenesis, tumor progression, and bone metabolism. To date, 15 semaphorins have been reported to be involved in the formation of the peripheral nervous system (PNS) in higher vertebrates. A number of experiments have revealed their functions in the PNS, where they act mainly as axonal guidance cues (as repellents or attractants). Semaphorins also play an important role in the migration of neurons and formation of sensory-motor connections in the PNS...
October 7, 2016: Cell Adhesion & Migration
Ana Gutiérrez-Franco, Herena Eixarch, Carme Costa, Vanessa Gil, Mireia Castillo, Laura Calvo-Barreiro, Xavier Montalban, José A Del Río, Carmen Espejo
Semaphorin 7A (sema7A) is classified as an immune semaphorin with dual functions in the immune system and in the central nervous system (CNS). These molecules are of interest due to their potential role in multiple sclerosis (MS), which is a chronic demyelinating and neurodegenerative disease of autoimmune origin. In this study, we elucidated the role of sema7A in neuroinflammation using both in vitro and in vivo experimental models. In an in vitro model of neuroinflammation, using cerebellar organotypic slice cultures, we observed that challenge with lipopolysaccharide (LPS) endotoxin did not affect demyelination or cell death in sema7A-deficient cultures compared to wild-type cultures...
October 6, 2016: Molecular Neurobiology
Jie-Xue Pan, Fang Wang, Long-Yun Ye
Semaphorins are essential for the functions in the regulation of cell migration. SEMA 4A has been proven to play a prominent role in immune function and angiogenesis. However, whether SEMA 4A is involved in HCC chemoresistance is unclear. We investigated the role of SEMA 4A in HCC chemoresistance and the underlying mechanisms. We tested the doxorubicin sensitivity of the Huh7, and Hep-G2 HCC cell lines. Immunofluorescence and Western blot were used to detect the location and expression of EMT-related protein, such as, E-cadherin, Vimentin, and SEMA4A expression...
October 28, 2016: Biochemical and Biophysical Research Communications
Teclise Ng, Catherine H H Hor, Benjamin Chew, Jing Zhao, Zhong Zhong, Jae Ryun Ryu, Eyleen L K Goh
Proper positioning of neurons is fundamental for brain functions. However, little is known on how adult-born neurons generated in the hilar side of hippocampal dentate gyrus (DG) migrate into the granular cell layer (GCL). Since class 3 Semaphorins (Sema3) are involved in dendritic growth of these newborn neurons, we examined if they are essential for cell positioning. We disrupted Sema3 signaling by silencing neuropilin 1 (NRP1) or 2 (NRP2), the main receptors for Sema3A and 3F, in neural progenitors of adult mouse DG...
September 29, 2016: Journal of Biological Chemistry
Deanna Gigliotti, Jeff R S Leiter, Peter B MacDonald, Jason Peeler, Judy E Anderson
BACKGROUND: Rotator-cuff injury (RCI) is common and painful; even after surgery, joint stability and function may not recover. Relative contributions to atrophy from disuse, fibrosis, denervation, and satellite-cell responsiveness to activating stimuli are not known. METHODS AND FINDINGS: Potential contributions of denervation and disrupted satellite cell responses to growth signals were examined in supraspinatus (SS) and control (ipsilateral deltoid) muscles biopsied from participants with RCI (N = 27)...
2016: PloS One
Hani Al-Shareef, Shin-Ichiro Hiraoka, Noriaki Tanaka, Yosuke Shogen, Atsushi-Doksa Lee, Sanam Bakhshishayan, Mikihiko Kogo
Lymph node (LN) metastasis has been suggested as a major prognostic factor for oral cancer. Knockdown of the growth factors and receptors involved in these metastatic mechanisms could significantly reduce LN metastasis and improve the survival of oral cancer patients after treatment. The present study, therefore, aimed to evaluate the expression levels of the following growth factors and receptors in squamous cell carcinoma (SCC) of the tongue: the vascular endothelial growth factor (VEGF)‑C and VEGF‑D, which bind to the cell surface tyrosine kinase receptor VEGF receptor‑3 (VEGFR‑3); C‑C motif chemokine receptor 7 (CCR7); neuropilin (NRP)1 and NRP2; and semaphorin 3E (SEMA3E)...
September 21, 2016: Oncology Reports
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