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https://www.readbyqxmd.com/read/29777213/semaphorin-6d-reverse-signaling-controls-macrophage-lipid-metabolism-and-anti-inflammatory-polarization
#1
Sujin Kang, Yoshimitsu Nakanishi, Yoshiyuki Kioi, Daisuke Okuzaki, Tetsuya Kimura, Hyota Takamatsu, Shohei Koyama, Satoshi Nojima, Masayuki Nishide, Yoshitomo Hayama, Yuhei Kinehara, Yasuhiro Kato, Takeshi Nakatani, Tomomi Shimogori, Junichi Takagi, Toshihiko Toyofuku, Atsushi Kumanogoh
Polarization of macrophages into pro-inflammatory or anti-inflammatory states has distinct metabolic requirements, with mechanistic target of rapamycin (mTOR) kinase signaling playing a critical role. However, it remains unclear how mTOR regulates metabolic status to promote polarization of these cells. Here we show that an mTOR-Semaphorin 6D (Sema6D)-Peroxisome proliferator receptor γ (PPARγ) axis plays critical roles in macrophage polarization. Inhibition of mTOR or loss of Sema6D blocked anti-inflammatory macrophage polarization, concomitant with severe impairments in PPARγ expression, uptake of fatty acids, and lipid metabolic reprogramming...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29748532/semaphorin-4d-correlates-with-increased-bone-resorption-hypercalcemia-and-disease-stage-in-newly-diagnosed-patients-with-multiple-myeloma
#2
Evangelos Terpos, Ioannis Ntanasis-Stathopoulos, Dimitrios Christoulas, Tina Bagratuni, Marios Bakogeorgos, Maria Gavriatopoulou, Evangelos Eleutherakis-Papaiakovou, Nikolaos Kanellias, Efstathios Kastritis, Meletios A Dimopoulos
Multiple myeloma (MM) is characterized by bone destruction due to increased bone resorption and decreased bone formation. Semaphorin 4D (CD100, Sema4D) is expressed by osteoclasts, binds to its receptor Plexin-B1, and acts as a mediator of osteoclast-osteoblast interaction that ultimately inhibits osteoblastic bone formation. Preclinical data suggest that Sema4D/Plexin-B1 pathway is implicated in MM-induced bone disease. However, there is no information on the role of Sema4D in MM patients. Thus, we evaluated Sema4D and Plexin-B1 in six myeloma cells lines in vitro; in the bone marrow plasma (BMP) and serum of 72 newly diagnosed symptomatic MM (NDMM) patients and in 25 healthy controls...
May 11, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29731509/a-genome-wide-association-study-for-extremely-high-intelligence
#3
D Zabaneh, E Krapohl, H A Gaspar, C Curtis, S H Lee, H Patel, S Newhouse, H M Wu, M A Simpson, M Putallaz, D Lubinski, R Plomin, G Breen
We used a case-control genome-wide association (GWA) design with cases consisting of 1238 individuals from the top 0.0003 (~170 mean IQ) of the population distribution of intelligence and 8172 unselected population-based controls. The single-nucleotide polymorphism heritability for the extreme IQ trait was 0.33 (0.02), which is the highest so far for a cognitive phenotype, and significant genome-wide genetic correlations of 0.78 were observed with educational attainment and 0.86 with population IQ. Three variants in locus ADAM12 achieved genome-wide significance, although they did not replicate with published GWA analyses of normal-range IQ or educational attainment...
May 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29714478/facile-synthesis-of-dimeric-thioether-macrocyclic-peptides-with-antibody-like-affinity-against-plexin-b1
#4
Nasir Bashiruddin, Yukiko Matsunaga, Masanobu Nagano, Junichi Takagi, Hiroaki Suga
Macrocyclic peptides have gained increasing attention due to their ease of discovery through various in vitro display platforms as well as their potential in possessing favorable properties of both small molecule and antibody drug classes. It is well known that the avidity achieved through the bivalent binding mode of antibodies gives rise to their slow dissociation rates and thus high potency as drug molecules. Here, we report the synthesis of dimeric thioether-macrocyclic peptides through a branched synthesis approach allowing for synthesis of dimeric peptides in a comparable number of steps as monomers and tunability of linker lengths from 30 Å to 200 Å...
May 1, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29702282/wedelolactone-inhibits-osteoclastogenesis-but-enhances-osteoblastogenesis-through-altering-different-semaphorins-production
#5
Xue Deng, Li-Na Liang, Di Zhu, Lu-Ping Zheng, Jing-Hua Yu, Xiang-Ling Meng, Yi-Ning Zhao, Xiao-Xin Sun, Tao-Wen Pan, Yan-Qiu Liu
Our previous study showed that wedelolactone, isolated from Ecliptae herba, enhanced osteoblastogenesis but inhibited osteoclastogenesis through Sema3A signaling pathway. This study aims to investigate the role of other semaphorins in wedelolactone-enhanced osteoblastogenesis and -inhibited osteoclastogenesis. Wedelolactone inhibited RANKL-induced Sema4D and Sema7A production, but had no effect on RANKL-reduced Sema6D expression in osteoclastic RAW264.7 cells. In mouse bone marrow mesenchymal stem cells (BMSC), wedelolactone reversed osteogenic medium(OS)-reduced Sema7A expression and OS-enhanced Sema3E mRNA expression, but no effect on OS-reduced Sema3B mRNA expression...
April 24, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29661844/plexin-a4-plexin-d1-complexes-convey-semaphorin-3c-signals-to-induce-cytoskeletal-collapse-in-the-absence-of-neuropilins
#6
Tatyana Smolkin, Inbal Nir-Zvi, Nerri Duvshani, Yelena Mumblat, Ofra Kessler, Gera Neufeld
Class-3 semaphorin guidance factors bind to receptor complexes containing neuropilin and plexin receptors. A semaphorin may bind to several receptor complexes containing somewhat different constituents, resulting in diverse effects on cell migration. U87MG glioblastoma cells express both neuropilins and the four class-A plexins. They respond by cytoskeletal collapse and cell contraction to sema3A or sema3B but fail to contract in response to Sema3C, Sema3D, Sema3G or sema3E even when class-A plexins are over-expressed in the cells...
April 16, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29642487/semaphorin-3c-and-its-receptors-in-cancer-and-cancer-stem-like-cells
#7
REVIEW
Jing Hao, Jennifer S Yu
Neurodevelopmental programs are frequently dysregulated in cancer. Semaphorins are a large family of guidance cues that direct neuronal network formation and are also implicated in cancer. Semaphorins have two kinds of receptors, neuropilins and plexins. Besides their role in development, semaphorin signaling may promote or suppress tumors depending on their context. Sema3C is a secreted semaphorin that plays an important role in the maintenance of cancer stem-like cells, promotes migration and invasion, and may facilitate angiogenesis...
April 8, 2018: Biomedicines
https://www.readbyqxmd.com/read/29620190/lncrnapcat29-inhibits-pulmonary-fibrosis-via-the-tgf%C3%A2-%C3%AE-1%C3%A2-regulated-rasal1-erk1-2-signal-pathway
#8
Xiaoming Liu, Shanyu Gao, Huile Xu
Pulmonary fibrosis is a severe respiratory disease characterized by the aggregation of extracellular matrix components and inflammation‑associated injury. Studies have suggested that long non‑coding RNAs (lncRNA) may serve a role in the pathophysiological processes of pulmonary fibrosis. However, the potential molecular mechanisms involving the lncRNA, prostate cancer‑associated transcript 29 (lncRNAPCAT29) in the progression of pulmonary fibrosis are yet to be determined. In the present study, the role of lncRNAPCAT29 and the potential signaling mechanism in pulmonary fibrosis progression was investigated...
March 28, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29520219/plexin-semaphorin-signaling-modifies-neuromuscular-defects-in-a-drosophila-model-of-peripheral-neuropathy
#9
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
https://www.readbyqxmd.com/read/29514220/long-non-coding-rna-casc2-inhibits-tumorigenesis-via-the-mir-181a-plxnc1-axis-in-melanoma
#10
Zhiqiong Wang, Xiaochuan Wang, Hongying Zhou, Xiao Dan, Lixiang Jiang, Yifei Wu
Melanoma is the most malignant and aggressive form of skin carcinoma originating in the pigment-producing melanocytes. In this study, to further investigate the molecular mechanisms of the development and progression of melanoma, we explored the impacts of long non-coding RNA (lncRNA) CASC2 on melanoma cell functions. Microarray analysis was carried out to identify the expression of lncRNA CASC2 in melanoma cells. MiR-181a was predicted as a sponging target of CASC2 by miRcode, while the 3'-UTR of Plexin C1 (PLXNC1) was a potential target of miR-181a according to the TargetScan database...
March 1, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29483957/overexpression-of-mical2-a-novel-tumor-promoting-factor-accelerates-tumor-progression-through-regulating-cell-proliferation-and-emt
#11
REVIEW
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
https://www.readbyqxmd.com/read/29464045/pathological-and-functional-significance-of-semaphorin-5a-in-pancreatic-cancer-progression-and-metastasis
#12
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
https://www.readbyqxmd.com/read/29420136/preparation-purification-and-identification-of-a-monoclonal-antibody-against-the-c-terminal-domain-of-semaphorin3f
#13
Pei-Pei Meng, Zhe Li, Sheng-Yu Wang, Wen-Wen Zhou, Malik Samiullah, Na Chen, Fang-Hong Luo, Ting Wu, Jiang-Hua Yan
Class three semaphorins were originally identified as mediators of axon guidance, which repelled axons and collapsed growth cones. As a member of class three semaphorins, semaphorin3F (Sema3F) has been found to have similar effects on tumor cells and endothelial cells and also is implicated in the signaling of tumor metastasis by forming a complex with neuropilins and plexins. In this study, our laboratory produced a monoclonal antibody against the C-terminal domain of Sema3F (Sema3Fc mAb) using the hybridoma method, expecting to explore the potential role of the antibody and its application in the detection of Sema3F...
February 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29378261/improving-the-quality-of-a-recombinant-rabbit-monoclonal-antibody-against-plxdc2-by-optimizing-transient-expression-conditions-and-purification-method
#14
Hisayo Shimizu, Masataka Nakagawa, Nemuri Todaka, Keitaro Imaizumi, Yasunori Kurosawa, Toshiaki Maruyama, C J Okumura, Takashi Shibata, Yosuke Tanaka, Yoshinori Sato, Yasuo Ono, Teruo Akuta
Rabbit monoclonal antibodies (mAbs) have many advantages over mouse antibodies in biological research and diagnostics applications because they exhibit high affinity and specificity. However, the methods of recombinant rabbit mAb production have not been optimized to the same extent as techniques used to produce mouse and human mAbs. In this study, we sought to optimize the production of a recombinant rabbit mAb against human plexin domain containing protein 2 (PLXDC2), a known cell surface antigen, by culturing HEK293-6E cells transfected with antibody-encoding genes at two different temperatures and by purifying the end-product by three different chromatography methods...
June 2018: Protein Expression and Purification
https://www.readbyqxmd.com/read/29377116/neural-regulation-of-bone-remodeling-identifying-novel-neural-molecules-and-pathways-between-brain-and-bone
#15
REVIEW
Shishu Huang, Zhenxia Li, Yunhui Liu, Dashuang Gao, Xinzhou Zhang, Jin Hao, Fan Yang
The metabolism and homeostasis of skeletal system has historically been regarded to be associated with the endocrine system. However, such view has been expanded with the recognition of several neural pathways playing important roles in the regulation of bone metabolism via central relays. In particular, bone metabolism and homeostasis has been reported to be precisely modulated by the central neural signaling. Initiated by the finding of leptin, the axis of neural regulation on bone expands rapidly. Semaphorin-plexin system play an important role in the crosstalk between osteoclasts and osteoblasts, a complex system has also been identified and includes neuropeptide Y and cannabinoids...
January 27, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29348142/sema3c-drives-cancer-growth-by-transactivating-multiple-receptor-tyrosine-kinases-via-plexin-b1
#16
James W Peacock, Ario Takeuchi, Norihiro Hayashi, Liangliang Liu, Kevin J Tam, Nader Al Nakouzi, Nastaran Khazamipour, Tabitha Tombe, Takashi Dejima, Kevin Ck Lee, Masaki Shiota, Daksh Thaper, Wilson Cw Lee, Daniel Hf Hui, Hidetoshi Kuruma, Larissa Ivanova, Parvin Yenki, Ivy Zf Jiao, Shahram Khosravi, Alice L-F Mui, Ladan Fazli, Amina Zoubeidi, Mads Daugaard, Martin E Gleave, Christopher J Ong
Growth factor receptor tyrosine kinase (RTK) pathway activation is a key mechanism for mediating cancer growth, survival, and treatment resistance. Cognate ligands play crucial roles in autocrine or paracrine stimulation of these RTK pathways. Here, we show SEMA3C drives activation of multiple RTKs including EGFR, ErbB2, and MET in a cognate ligand-independent manner via Plexin B1. SEMA3C expression levels increase in castration-resistant prostate cancer (CRPC), where it functions to promote cancer cell growth and resistance to androgen receptor pathway inhibition...
February 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29322779/mining-the-secretome-of-c2c12-muscle-cells-data-dependent-experimental-approach-to-analyze-protein-secretion-using-label-free-quantification-and-peptide-based-analysis
#17
Leonie Grube, Rafael Dellen, Fabian Kruse, Holger Schwender, Kai Stühler, Gereon Poschmann
Secretome analysis faces several challenges including detection of low abundant proteins and the discrimination of bona fide secreted proteins from false-positive identifications stemming from cell leakage or serum. Here, we developed a two-step secretomics approach and applied it to the analysis of secreted proteins of C2C12 skeletal muscle cells since the skeletal muscle has been identified as an important endocrine organ secreting myokines as signaling molecules. First, we compared culture supernatants with corresponding cell lysates by mass spectrometry-based proteomics and label-free quantification...
February 2, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29320740/plexina2-forward-signaling-through-rap1-gtpases-regulates-dentate-gyrus-development-and-schizophrenia-like-behaviors
#18
Xiao-Feng Zhao, Rafi Kohen, Rachel Parent, Yuntao Duan, Grace L Fisher, Matthew J Korn, Lingchao Ji, Guoqiang Wan, Jing Jin, Andreas W Püschel, David F Dolan, Jack M Parent, Gabriel Corfas, Geoffrey G Murphy, Roman J Giger
Dentate gyrus (DG) development requires specification of granule cell (GC) progenitors in the hippocampal neuroepithelium, as well as their proliferation and migration into the primordial DG. We identify the Plexin family members Plxna2 and Plxna4 as important regulators of DG development. Distribution of immature GCs is regulated by Sema5A signaling through PlxnA2 and requires a functional PlxnA2 GTPase-activating protein (GAP) domain and Rap1 small GTPases. In adult Plxna2-/- but not Plxna2-GAP-deficient mice, the dentate GC layer is severely malformed, neurogenesis is compromised, and mossy fibers form aberrant synaptic boutons within CA3...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29214018/transcriptional-changes-in-mesenteric-and-subcutaneous-adipose-tissue-from-holstein-cows-in-response-to-plane-of-dietary-energy
#19
S J Moisá, P Ji, J K Drackley, S L Rodriguez-Zas, J J Loor
Background: Dairy cows can readily overconsume dietary energy during most of the prepartum period, often leading to higher prepartal concentrations of insulin and glucose and excessive body fat deposition. The end result of these physiologic changes is greater adipose tissue lipolysis post-partum coupled with excessive hepatic lipid accumulation and compromised health. Although transcriptional regulation of the adipose response to energy availability is well established in non-ruminants, such regulation in cow adipose tissue depots remains poorly characterized...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29203829/il-4-driven-transcription-factor-foxq1-is-expressed-by-monocytes-in-atopic-dermatitis-and-stimulates-monocyte-migration
#20
Ilja Ovsiy, Vladimir Riabov, Ioannis Manousaridis, Julia Michel, Kondaiah Moganti, Shuiping Yin, Tengfei Liu, Carsten Sticht, Elisabeth Kremmer, Martin C Harmsen, Sergij Goerdt, Alexei Gratchev, Julia Kzhyshkowska
Monocytes are actively recruited at sites of chronic inflammation. However, molecular factors involved in this process are not fully elucidated. Here, we show that cytokine IL-4 which is implicated in the development of chronic inflammatory disease atopic dermatitis (AD) induces expression of transcription factor FoxQ1 in human monocytes and macrophages. FoxQ1 mRNA levels were elevated in monocytes of AD patients compared to healthy donors. Overexpression of FoxQ1 in RAW 264.7 monocytic cells facilitated their migration towards MCP-1 and was associated with decreased expression of migration-regulating genes (claudin 11 and plexin C1)...
December 4, 2017: Scientific Reports
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