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https://www.readbyqxmd.com/read/27900574/mast-cell-glycosaminoglycans
#1
REVIEW
B Mulloy, R Lever, C P Page
Mast cells contain granules packed with a mixture of proteins that are released on degranulation. The proteoglycan serglycin carries an array of glycosaminoglycan (GAG) side chains, sometimes heparin, sometimes chondroitin or dermatan sulphate. Tight packing of granule proteins is dependent on the presence of serglycin carrying these GAGs. The GAGs of mast cells were most intensively studied in the 1970s and 1980s, and though something is known about the fine structure of chondroitin sulphate and dermatan sulphate in mast cells, little is understood about the composition of the heparin/heparan sulphate chains...
November 30, 2016: Glycoconjugate Journal
https://www.readbyqxmd.com/read/27819672/serglycin-in-tumor-microenvironment-promotes-non-small-cell-lung-cancer-aggressiveness-in-a-cd44-dependent-manner
#2
J-Y Guo, H-S Hsu, S-W Tyan, F-Y Li, J-Y Shew, W-H Lee, J-Y Chen
Tumor microenvironment (TME) plays an active role in promoting tumor progression. To further understand the communication between TME and tumor cells, this study aimed at investigating the involvement of CD44, a type I cell surface receptor, in the crosstalk between tumor cells and TME. We have previously shown that chondroitin sulfate proteoglycan serglycin (SRGN), a CD44-interacting factor, was preferentially secreted by cancer-associated fibroblasts (CAFs) for promoting tumor growth in breast cancer patients...
November 7, 2016: Oncogene
https://www.readbyqxmd.com/read/27809309/extracellular-serglycin-upregulates-the-cd44-receptor-in-an-autocrine-manner-to-maintain-self-renewal-in-nasopharyngeal-carcinoma-cells-by-reciprocally-activating-the-mapk-%C3%AE-catenin-axis
#3
Qiaoqiao Chu, Hongbing Huang, Tiejun Huang, Li Cao, Lixia Peng, Simei Shi, Lisheng Zheng, Liang Xu, Shijun Zhang, Jialing Huang, Xinjian Li, Chaonan Qian, Bijun Huang
Serglycin is a proteoglycan that was first found to be secreted by hematopoietic cells. As an extracellular matrix (ECM) component, serglycin promotes nasopharyngeal carcinoma (NPC) metastasis and serves as an independent, unfavorable NPC prognostic indicator. The detailed mechanism underlying the roles of serglycin in cancer progression remains to be clarified. Here, we report that serglycin knockdown in NPC cells inhibited cell sphere formation and tumor seeding abilities. Serglycin downregulation enhanced high-metastasis NPC cell sensitivity to chemotherapy...
November 3, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27445159/bioengineered-human-heparin-with-anticoagulant-activity
#4
Megan S Lord, Bill Cheng, Fengying Tang, J Guy Lyons, Jelena Rnjak-Kovacina, John M Whitelock
Heparin is a carbohydrate anticoagulant used clinically to prevent thrombosis, however impurities can limit its efficacy. Here we report the biosynthesis of heparin-like heparan sulfate via the recombinant expression of human serglycin in human cells. The expressed serglycin was also decorated with chondroitin/dermatan sulfate chains and the relative abundance of these glycosaminoglycan chains changed under different concentrations of glucose in the culture medium. The recombinantly expressed serglycin produced with 25mM glucose present in the culture medium was found to possess anticoagulant activity one-seventh of that of porcine unfractionated heparin, demonstrating that bioengineered human heparin-like heparan sulfate may be a safe next-generation pharmaceutical heparin...
July 18, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27267469/serglycin-proteoglycans-limit-enteropathy-in-trichinella-spiralis-infected-mice
#5
Ananya Roy, Osama Sawesi, Ulrika Pettersson, Anders Dagälv, Lena Kjellén, Anna Lundén, Magnus Åbrink
BACKGROUND: Serglycin proteoglycans are essential for maturation of secretory granules and for the correct granular storage of cationic proteases in hematopoietic cells, e.g. mast cells. However, little is known about the in vivo functions of serglycin proteoglycans during infection. Here we investigated the potential role of serglycin proteoglycans in host defense after infection with the nematode Trichinella spiralis. RESULTS: Twelve days post infection lack of serglycin proteoglycans caused significantly increased enteropathy...
2016: BMC Immunology
https://www.readbyqxmd.com/read/27223472/targeting-serglycin-prevents-metastasis-in-murine-mammary-carcinoma
#6
Ananya Roy, Julia Femel, Elisabeth J M Huijbers, Dorothe Spillmann, Erik Larsson, Maria Ringvall, Anna-Karin Olsson, Magnus Åbrink
In hematopoietic cells, serglycin proteoglycans mainly contribute to proper storage and secretion of inflammatory mediators via their negatively charged glycosaminoglycans. Serglycin proteoglycans are also expressed in cancer cells where increased expression has been linked to poor prognosis. However, the serglycin-dependent mediators promoting cancer progression remain to be determined. In the present study we report that genetic ablation of serglycin proteoglycan completely blocks lung metastasis in the MMTV-PyMT-driven mouse breast cancer model, while serglycin-deficiency did not affect primary tumour growth or number of mammary tumours...
2016: PloS One
https://www.readbyqxmd.com/read/27179695/estrogen-receptor-beta-modulates-breast-cancer-cells-functional-properties-signaling-and-expression-of-matrix-molecules
#7
Zoi Piperigkou, Panagiotis Bouris, Maurizio Onisto, Marco Franchi, Dimitris Kletsas, Achilleas D Theocharis, Nikos K Karamanos
Estrogen receptors have pivotal roles in breast cancer growth and progression. ERα has been clearly shown to play key role in hormone-dependent breast cancer properties, but little is known for the isoform ERβ. To evaluate the role of ERβ, we established stably transfected ERβ-suppressed MDA-MB-231 breast cancer cells by knocking down the human ERβ gene, using specific shRNA lentiviral particles. As observed by scanning electron microscopy, the ERβ suppression induces significant phenotypic changes in these cells, as compared to the control cells...
May 11, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27042303/il-6-and-il-17a-degradation-by-mast-cells-is-mediated-by-a-serglycin-serine-protease-axis
#8
Ida Waern, Iulia Karlsson, Gunnar Pejler, Sara Wernersson
Mast cells contain large amounts of fully active proteases that are stored in complex with serglycin proteoglycan in their secretory granules. Upon degranulation, such serglycin:protease complexes are released to the extracellular space and can potentially have an impact on the local inflammatory reaction, either through direct effects of serglycin proteoglycan or through effects mediated by its bound proteases. The objective of this study was to address this scenario by investigating the possibility that serglycin-associated proteases can regulate levels of pro-inflammatory cytokines...
March 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/26756195/serglycin-determines-secretory-granule-repertoire-and-regulates-natural-killer-cell-and-cytotoxic-t-lymphocyte-cytotoxicity
#9
Vivien R Sutton, Amelia J Brennan, Sarah Ellis, Jill Danne, Kevin Thia, Misty R Jenkins, Ilia Voskoboinik, Gunnar Pejler, Ricky W Johnstone, Daniel M Andrews, Joseph A Trapani
The anionic proteoglycan serglycin is a major constituent of secretory granules in cytotoxic T lymphocyte (CTL)/natural killer (NK) cells, and is proposed to promote the safe storage of the mostly cationic granule toxins, granzymes and perforin. Despite the extensive defects of mast cell function reported in serglycin gene-disrupted mice, no comprehensive study of physiologically relevant CTL/NK cell populations has been reported. We show that the cytotoxicity of serglycin-deficient CTL and NK cells is severely compromised but can be partly compensated in both cell types when they become activated...
March 2016: FEBS Journal
https://www.readbyqxmd.com/read/26755884/proteoglycans-in-liver-cancer
#10
REVIEW
Kornélia Baghy, Péter Tátrai, Eszter Regős, Ilona Kovalszky
Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types...
January 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/26694746/serglycin-in-quiescent-and-proliferating-primary-endothelial-cells
#11
Trine M Reine, Tram T Vuong, Arkady Rutkovskiy, Astri J Meen, Jarle Vaage, Trond G Jenssen, Svein O Kolset
Proteoglycans are fundamental components of the endothelial barrier, but the functions of the proteoglycan serglycin in endothelium are less described. Our aim was to describe the roles of serglycin in processes relevant for endothelial dysfunction. Primary human umbilical vein endothelial cells (HUVEC) were cultured in vitro and the expression of proteoglycans was investigated. Dense cell cultures representing the quiescent endothelium coating the vasculature was compared to sparse activated cell cultures, relevant for diabetes, cancer and cardiovascular disease...
2015: PloS One
https://www.readbyqxmd.com/read/26692491/intestinal-and-peritoneal-mast-cells-differ-in-kinetics-of-quantal-release
#12
COMPARATIVE STUDY
Santiago Balseiro-Gomez, M Pilar Ramirez-Ponce, Jorge Acosta, Eva Ales, Juan A Flores
5-hydroxytriptamine (5-HT, serotonin) storage and release in mast cell (MC) secretory granules (SG) are dependent on serglycin proteoglycans (PG). This notion is based on the studies of MC of the connective tissue subtype that predominantly contain PG of the heparin type, whereas intestinal mucosal MC, which contain predominantly chondroitin sulfate, have been poorly explored. In the present study, we addressed the possibility that PG contents may differently affect the storage and release of preformed mediators in these two MC subclasses and explain in part their different functional properties...
January 15, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26626992/lin-cd34hi-cd117int-hi-fc%C3%AE%C2%B5ri-cells-in-human-blood-constitute-a-rare-population-of-mast-cell-progenitors
#13
Joakim S Dahlin, Andrei Malinovschi, Helena Öhrvik, Martin Sandelin, Christer Janson, Kjell Alving, Jenny Hallgren
Mast cells are rare tissue-resident immune cells that are involved in allergic reactions, and their numbers are increased in the lungs of asthmatics. Murine lung mast cells arise from committed bone marrow-derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in the tissue. In humans, mast cells can be cultured from multipotent CD34(+) progenitor cells. However, a population of distinct precursor cells that give rise to mast cells has remained undiscovered...
January 28, 2016: Blood
https://www.readbyqxmd.com/read/26581653/increased-expression-of-serglycin-in-specific-carcinomas-and-aggressive-cancer-cell-lines
#14
Angeliki Korpetinou, Dionysios J Papachristou, Angeliki Lampropoulou, Panagiotis Bouris, Vassiliki T Labropoulou, Argyrios Noulas, Nikos K Karamanos, Achilleas D Theocharis
In the present pilot study, we examined the presence of serglycin in lung, breast, prostate, and colon cancer and evaluated its expression in cell lines and tissues. We found that serglycin was expressed and constitutively secreted in culture medium in high levels in more aggressive cancer cells. It is worth noticing that aggressive cancer cells that harbor KRAS or EGFR mutations secreted serglycin constitutively in elevated levels. Furthermore, we detected the transcription of an alternative splice variant of serglycin lacking exon 2 in specific cell lines...
2015: BioMed Research International
https://www.readbyqxmd.com/read/26527314/proteoglycan-expression-correlates-with-the-phenotype-of-malignant-and-non-malignant-ebv-positive-b-cell-lines
#15
Alexandra Y Tsidulko, Liudmila Matskova, Lidiia A Astakhova, Ingemar Ernberg, Elvira V Grigorieva
The involvement of proteoglycans (PGs) in EBV-host interactions and lymphomagenesis remains poorly investigated. In this study, expression of major proteoglycans (syndecan-1, glypican-1, perlecan, versican, brevican, aggrecan, NG2, serglycin, decorin, biglycan, lumican, CD44), heparan sulphate (HS) metabolic system (EXT1/2, NDST1/2, GLCE, HS2ST1, HS3ST1/2, HS6ST1/2, SULF1/2, HPSE) and extracellular matrix (ECM) components (collagen 1A1, fibronectin, elastin) in primary B cells and EBV carrying cell lines with different phenotypes, patterns of EBV-host cell interaction and viral latency stages (type I-III) was investigated...
December 22, 2015: Oncotarget
https://www.readbyqxmd.com/read/26391682/serglycin-protects-against-high-fat-diet-induced-increase-in-serum-ldl-in-mice
#16
Astri J Meen, Christian A Drevon, Gunnar Pejler, Trond G Jenssen, Ole Kristoffer Olstad, Magnus Åbrink, Svein O Kolset
Proteoglycans have been implicated in regulation of lipoprotein metabolism. However, the impact of serglycin, the major proteoglycan expressed by many hematopoietic- and endothelial cells, on lipoprotein metabolism has not been explored. Here we addressed this issue by comparing several parameters of lipid metabolism in wild type (WT) and serglycin-/- mice, both at baseline and after feeding mice the Paigen diet. We show that, after feeding this diet for 20 weeks, serglycin deficient mice exhibited elevated concentrations of serum LDL in comparison with WT mice, thus suggesting that serglycin protects against an elevation of serum LDL levels after intake of a high-fat diet...
December 2015: Glycoconjugate Journal
https://www.readbyqxmd.com/read/26290530/the-effect-of-acute-and-long-term-physical-activity-on-extracellular-matrix-and-serglycin-in-human-skeletal-muscle
#17
Marit Hjorth, Frode Norheim, Astri J Meen, Shirin Pourteymour, Sindre Lee, Torgeir Holen, Jørgen Jensen, Kåre I Birkeland, Vladimir N Martinov, Torgrim M Langleite, Kristin Eckardt, Christian A Drevon, Svein O Kolset
Remodeling of extracellular matrix (ECM), including regulation of proteoglycans in skeletal muscle can be important for physiological adaptation to exercise. To investigate the effects of acute and long-term exercise on the expression of ECM-related genes and proteoglycans in particular, 26 middle-aged, sedentary men underwent a 12 weeks supervised endurance and strength training intervention and two acute, 45 min bicycle tests (70% VO2max), one at baseline and one after 12 weeks of training. Total gene expression in biopsies from m...
August 2015: Physiological Reports
https://www.readbyqxmd.com/read/26107406/rapid-endolysosomal-escape-and-controlled-intracellular-trafficking-of-cell-surface-mimetic-quantum-dots-anchored-peptides-and-glycopeptides
#18
Roger S Tan, Kentaro Naruchi, Maho Amano, Hiroshi Hinou, Shin-Ichiro Nishimura
A novel strategy for the development of a high performance nanoparticules platform was established by means of cell surface mimetic quantum-dots (QDs)-anchored peptides/glycopeptides, which was developed as a model system for nanoparticle-based drug delivery (NDD) vehicles with defined functions helping the specific intracellular trafficking after initial endocytosis. In this paper, we proposed a standardized protocol for the preparation of multifunctional QDs that allows for efficient cellular uptake and rapid escaping from the endolysosomal system and subsequent cytoplasmic molecular delivery to the target cellular compartment...
September 18, 2015: ACS Chemical Biology
https://www.readbyqxmd.com/read/25978773/loss-of-serglycin-promotes-primary-tumor-growth-and-vessel-functionality-in-the-rip1-tag2-mouse-model-for-spontaneous-insulinoma-formation
#19
Andrew Hamilton, Vladimir Basic, Sandra Andersson, Magnus Abrink, Maria Ringvall
The serglycin proteoglycan is mainly expressed by hematopoietic cells where the major function is to retain the content of storage granules and vesicles. In recent years, expression of serglycin has also been found in different forms of human malignancies and a high serglycin expression level has been correlated with a more migratory and invasive phenotype in the case of breast cancer and nasopharyngeal carcinoma. Serglycin has also been implicated in the development of the tumor vasculature in multiple myeloma and hepatocellular carcinoma where reduced expression of serglycin was correlated with a less extensive vasculature...
2015: PloS One
https://www.readbyqxmd.com/read/25892563/heparin-interaction-with-a-receptor-on-hyperglycemic-dividing-cells-prevents-intracellular-hyaluronan-synthesis-and-autophagy-responses-in-models-of-type-1-diabetes
#20
REVIEW
Aimin Wang, Nehru Viji Sankaranarayanan, Masaki Yanagishita, Douglas M Templeton, Umesh R Desai, Kazuyuki Sugahara, Christina P Wang, Vincent C Hascall
Previous studies and ongoing research indicate the importance of an interaction between a putative receptor on dividing cells in hyperglycemia and the non-reducing end motifs of heparin stored in mast cell secretory granules and how this interaction prevents activation of hyaluronan synthesis in intracellular compartments and subsequent autophagy. This suggests a new role for endosomal heparanase in exposing this cryptic motif present in the initial large heparin chains on serglycin and in the highly sulfated (NS) domains of heparan sulfate...
October 2015: Matrix Biology: Journal of the International Society for Matrix Biology
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