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Li Liu, Jue Wang, Xiaomeng Song, Qingping Zhu, Shuping Shen, Wei Zhang
The aim of the present study was to investigate the role of Semaphorin 3A (Sema3A) in the osteogenic differentiation of human alveolar bone marrow mesenchymal stem cells (hABMMSCs). To investigate whether Sema3A affects hABMMSC proliferation and osteogenic differentiation, a stable Sema3A-overexpression cell line was generated by infection with the pAdCMV-SEMA3A-MCS-EGFP vector. Cell counting kit-8 and clone formation assays were performed to determine the proliferation ability of hABMMSCs, while cell osteogenic differentiation was assayed using Alizarin Red S staining...
April 2018: Experimental and Therapeutic Medicine
Roshanak Derakhshandeh, Sonia Sanadhya, Kyu Lee Han, Haiyan Chen, Olga Goloubeva, Tonya J Webb, Rania H Younis
The search for stromal biomarkers in carcinoma patients is a challenge in the field. Semaphorin 4D (Sema4D), known for its various developmental, physiological and pathological effects, plays a role in pro and anti-inflammatory responses. It is expressed in many epithelial tumors including head and neck squamous cell carcinoma (HNSCC). Recently, we found that HNSCC-associated Sema4D modulates an immune-suppressive, tumor-permissible environment by inducing the expansion of myeloid derived suppressor cells. The purpose of this study was to determine the value of Sema4D as a biomarker for the peri-tumoral stromal phenotype in human HNSCC...
February 16, 2018: Oncotarget
Wei Fang, Ziying Wang, Quanxin Li, Xiaojie Wang, Yan Zhang, Yu Sun, Wei Tang, Chunhong Ma, Jinpeng Sun, Ningjun Li, Fan Yi
Background G protein-coupled receptors (GPCRs) participate in a variety of physiologic functions, and several GPCRs have critical physiologic and pathophysiologic roles in the regulation of renal function. We investigated the role of Gpr97, a newly identified member of the adhesion GPCR family, in AKI. Methods AKI was induced by ischemia-reperfusion or cisplatin treatment in Gpr97-deficient mice. We assessed renal injury in these models and in patients with acute tubular necrosis by histologic examination, and we conducted microarray analysis and in vitro assays to determine the molecular mechanisms of Gpr97 function...
March 12, 2018: Journal of the American Society of Nephrology: JASN
Nadav Willner, Yair Goldberg, Elad Schiff, Zahava Vadasz
AIMS: Semaphorin 4D (Sema4D) is expressed on platelets and T-cells and known to be involved in inflammation. The aims of this study include comparing Sema4D and N terminal pro brain natriuretic peptide (NT-proBNP) serum levels in heart failure (HF) patients to a control group, evaluating the correlation between Sema4D and NT-proBNP levels, and assessing Sema4D serum levels in HF patients during acute exacerbation and remission. METHODS AND RESULTS: Forty-five patients diagnosed with HF (based on echocardiographic findings, positive NT-proBNP levels, and normal C-reactive protein) and 11 healthy controls (declaring no chronic diseases or medications) comprised the study population...
March 10, 2018: ESC Heart Failure
Stuart J Grice, James N Sleigh, M Zameel Cader
Dominant mutations in GARS , encoding the ubiquitous enzyme glycyl-tRNA synthetase (GlyRS), cause peripheral nerve degeneration and Charcot-Marie-Tooth disease type 2D (CMT2D). This genetic disorder exemplifies a recurring paradigm in neurodegeneration, in which mutations in essential genes cause selective degeneration of the nervous system. Recent evidence suggests that the mechanism underlying CMT2D involves extracellular neomorphic binding of mutant GlyRS to neuronally-expressed proteins. Consistent with this, our previous studies indicate a non-cell autonomous mechanism, whereby mutant GlyRS is secreted and interacts with the neuromuscular junction (NMJ)...
2018: Frontiers in Molecular Neuroscience
Li Ning, Zhiguo Li, Dianjun Wei, Haiyan Chen, Chao Yang, Dawei Wu, Yanchun Wang, Jingwei Zhang
Contrast-induced acute kidney injury (CI-AKI) is a serious complication of diagnostic coronary angiograph and percutaneous coronary intervention (PCI). However, the exact pathophysiological mechanisms underlying CI-AKI development are largely unknown. The present study examined whether urinary semaphorin 3A levels predict the development of CI-AKI in patients undergoing PCI. This study enrolled 168 patients with stable angina undergoing elective PCI. Serial urine samples, obtained at baseline and 2, 6, 12, 24, 36, and 48 h post-PCI were analyzed by semaphorin 3A and neutrophil gelatinase-associated lipocalin (NGAL) ELISA kit...
March 1, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
T-J Liu, J-L Guo, H-K Wang, X Xu
OBJECTIVE: Oral tongue squamous cell carcinoma (OTSCC) is the most frequently encountered malignant epithelial tumors. Semaphorin-7A is a membrane-associated/secreted protein that plays an essential role in the migration and progression of human malignancies. We aimed to investigate the mechanisms of Semaphorin-7A in the growth and migration of OTSCC. MATERIALS AND METHODS: The expressions of Semaphorin-7A in cells were tested by RT-PCR, Western blot, and Immunofluorescence, separately...
February 2018: European Review for Medical and Pharmacological Sciences
Vera S Donnenberg, Jayce Jieming Zhang, Erika Moravcikova, Ernest Michael Meyer, Haihui Lu, Christian T Carson, Albert D Donnenberg
Flow cytometric cell surface proteomics provides a new and powerful tool to determine changes accompanying neoplastic transformation and invasion, providing clues to essential interactions with the microenvironment as well as leads for potential therapeutic targets. One of the most important advantages of flow cytometric cell surface proteomics is that it can be performed on living cells that can be sorted for further characterization and functional studies. Here, we document the surface proteome of clonogenic metastatic breast cancer (MBrCa) explants, which was strikingly similar to that of normal mesenchymal stromal cells (P = 0...
March 2, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Hongqiang Yu, Tingting Pei, Jingyi Ren, Ye Ding, Anqian Wu, Yanmin Zhou
Bone remodeling is under the control of various signals and systems in the body, including the nervous system. Semaphorin (Sema) 3A is a chemorepellent protein which regulates bone mass. Schwann cells, having a pivotal role following nerve injury, interact with Sema3A under numerous circumstances. The present study established a co‑culture system of MG63 and Schwann cells to investigate the role of the interaction between Sema3A and Schwann cells in osteogenesis. The results from the alkaline phosphatase assay, calcium nodule staining and the analysis of the osteogenic gene expression revealed that Sema3A inhibits osteogenic differentiation of MG63 cells in single‑cell culture and promotes osteogenic differentiation of MG63 cells in co‑culture with Schwann cells, in a concentration‑dependent manner...
February 22, 2018: Molecular Medicine Reports
Yongqiang Cai, Jinping Lu, Faqing Tang
Molecule interacting with CasL 2 (MICAL2), a microtubule associated monooxygenase, is involved in cell growth, axon guidance, vesicle trafficking and apoptosis. Recent studies have demonstrated that MICAL2 is highly expressed in tumor and accelerates tumor progression and it is deemed to be a novel tumor-promoting factor. MICAL2 overexpression increases cell proliferation to accelerate tumor growth, and MICAL2 also promotes epithelial-mesenchymal transition (EMT)-related proteins to increase cancer cell metastasis...
2018: Journal of Cancer
Takuya Sumi, Tsuyoshi Imasaki, Mari Aoki, Naoki Sakai, Eriko Nitta, Mikako Shirouzu, Ryo Nitta
Collapsin response mediator protein 2 (CRMP2) regulates neuronal polarity by controlling microtubule dynamics. CRMP2 activity is regulated by semaphorin-induced phosphorylation at the C-terminal tail domain. Unphosphorylated CRMP2 induces effective axonal microtubule formation to give the axonal characteristics to a neurite, whereas phosphorylated CRMP2 leads to the apparently opposite effect, growth cone collapse. We have recently characterized the structural detail of CRMP2-induced axonal microtubule formation (Niwa et al...
2018: Cell Structure and Function
Boris Chaumette, Oussama Kebir, Juliette Pouch, Bertrand Ducos, Fekrije Selimi, Raphael Gaillard, Marie-Odile Krebs
The biological processes associated with the onset of schizophrenia remain largely unknown. Current hypotheses favor gene × environment interactions as supported by our recent report about DNA methylation changes during the onset of psychosis. Here, we conducted the first longitudinal transcriptomic analysis of blood samples from 31 at-risk individuals who later converted to psychosis and 63 at-risk individuals who did not. Individuals were followed for a maximum of 1 year. Blood samples were collected at baseline and at the end of follow-up and individuals served as their own controls...
February 17, 2018: Schizophrenia Bulletin
Man Wai Tang, Beatriz Malvar Fernández, Simon P Newsom, Jaap D van Buul, Timothy R D J Radstake, Dominique L Baeten, Paul P Tak, Kris A Reedquist, Samuel García
Objective: Class 3 semaphorins regulate diverse cellular processes relevant to the pathology of RA, including immune modulation, angiogenesis, apoptosis and invasive cell migration. Therefore, we analysed the potential role of class 3 semaphorins in the pathology of RA. Methods: Protein and mRNA expression in RA synovial tissue, SF and fibroblast-like synoviocytes (FLS) were determined by immunoblotting and quantitative PCR (qPCR). RA FLS migration and invasion were determined using wound closure and transwell invasion assays, respectively...
February 19, 2018: Rheumatology
Ning Lu, Ying Li, Zhiqiang Zhang, Junji Xing, Ying Sun, Sheng Yao, Lieping Chen
Semaphorin-4A (Sema4A) has been implicated in the co-stimulation of T cells and drives Th1 immune responses by binding to the receptor T-cell immunoglobulin and mucin domain protein 2 (Tim-2) in mice. Here we show that human, but not murine, Sema4A is preferentially expressed on antigen-presenting cells, and co-stimulates CD4+ T-cell proliferation and drives Th2 responses. By employing two independent cloning strategies, we demonstrate that Immunoglobulin-like transcript 4 (ILT-4) is a receptor for human SEMA4A (hSEMA4A) on activated CD4+ T cells...
February 21, 2018: Nature Communications
Sugandha Saxena, Yuri Hayashi, Lingyun Wu, Mohammad Awaji, Pranita Atri, Michelle L Varney, Abhilasha Purohit, Satyanarayana Rachagani, Surinder K Batra, Rakesh K Singh
Semaphorin-5A (SEMA5A) has differential cell surface expression between normal and cancer cells and represents an attractive target for therapeutic intervention in pancreatic cancer (PC). In this study, we delineated the pathological expression and significance of SEMA5A during PC progression and metastasis. We utilized human tissue microarrays and different PC mouse models (Pdx1-cre; LSL- Kras(G12D) , Pdx1-Cre; LSL-Kras(G12D) ; LSL-p53(R172H) and RIP1-Tag2) to analyze SEMA5A expression during PC progression...
January 19, 2018: Oncotarget
Xiao Chen, Hailing Wang, Kui Jia, Hao Wang, Tao Ren
Pulmonary inflammation is a primary characteristic of lung injury initiated by the accession of immune cells into the alveolar space. Neutrophil migration serves an important role in pulmonary inflammation mediated by the migration of neutrophils into hypoxic tissue sites. The elimination of pulmonary inflammation is directly associated with rehabilitation in patients with lung injury. Anti-inflammatory treatment is essential following lung injury and ultimately determines patient outcomes. Semaphorin-7A (SEMA-7A) is a member of the Semaphorin family that influences the migration of neutrophils into hypoxic tissue sites, thus promoting inflammation...
March 2018: Experimental and Therapeutic Medicine
Yashang Lee, Katrina Lehmann Blount, Feng Dai, Siobhan Thompson, Jonathan Kaufman Scher, Sherrie Bitterman, Madeline Droher, Erica L Herzog, Gilbert Moeckel, Anil Karihaloo, Neera K Dahl
BACKGROUND: Semaphorin 7A (SEMA7A) is an immunomodulating protein implicated in lung and liver fibrosis. In autosomal-dominant polycystic kidney disease (ADPKD), the progressive expansion of renal cysts, inflammation, and subsequent renal fibrosis leads to end-stage renal disease (ESRD). SEMA7A may play a role in renal fibrosis and in ADPKD. METHODS: We evaluated Sema7a in a mouse model of renal fibrosis and determined the expression of SEMA7A in human ADPKD kidney...
February 16, 2018: Clinical and Experimental Nephrology
Gustavo Dias Ferreira, Edison Capp, Julia Jauckus, Thomas Strowitzki, Ariane Germeyer
PURPOSE: The semaphorins are related to angiogenesis and cell proliferation depending on the tissue. The purpose of this study was to assess gene expression of class 3 semaphorin (SEMA3A-F) and protein expression of semaphorin 3A (SEMA3A) within human endometrium throughout the menstrual cycle. METHODS: Gene expression of SEMA3A-F was analyzed by real-time PCR (qRT-PCR) and protein expression of SEMA3A was analyzed by ELISA in endometrial biopsies in the proliferative and secretory phase of the menstrual cycle...
February 15, 2018: Archives of Gynecology and Obstetrics
Anastasya Birger, Miri Ottolenghi, Liat Perez, Benjamin Reubinoff, Oded Behar
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by cell death of upper and lower motor neurons (MNs). The cause of MN cell loss is not completely understood but involves both cell autonomous and non-cell autonomous mechanisms. Numerous molecules have been implicated to be involved in the death of MNs. One such candidate is semaphorin 3A (Sema3A). In ALS patients, Sema3A was shown to be significantly upregulated in the motor cortex and downregulated in the spinal cord. In the mouse, Sema3A was shown to be an axon repellent molecule for MNs...
February 15, 2018: Cell Death & Disease
Maciej Daniszewski, Anne Senabouth, Quan H Nguyen, Duncan E Crombie, Samuel W Lukowski, Tejal Kulkarni, Valentin M Sluch, Jafar S Jabbari, Xitiz Chamling, Donald J Zack, Alice Pébay, Joseph E Powell, Alex W Hewitt
We used single cell sequencing technology to characterize the transcriptomes of 1,174 human embryonic stem cell-derived retinal ganglion cells (RGCs) at the single cell level. The human embryonic stem cell line BRN3B-mCherry (A81-H7), was differentiated to RGCs using a guided differentiation approach. Cells were harvested at day 36 and prepared for single cell RNA sequencing. Our data indicates the presence of three distinct subpopulations of cells, with various degrees of maturity. One cluster of 288 cells showed increased expression of genes involved in axon guidance together with semaphorin interactions, cell-extracellular matrix interactions and ECM proteoglycans, suggestive of a more mature RGC phenotype...
February 13, 2018: Scientific Data
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