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Kenan Özler
BACKGROUND: The first research to determine synovial fluid ADAMTS4 and serglycin levels in osteoarthritis and OA progression. AIM: We aimed to determine ADAMTS4 and serglycin levels, interactions, and changes in the synovial fluid of knee OA, and also to determine effective in OA progression. METHODS: A case-control study was carried out including a total of 88 participants (29 patients late OA [LOA], 28 early OA [EOA], and 30 controls). Synovial fluid serglycin and ADAMTS4 levels were measured by commercially available ELISA kits, and knee functions of the patients were evaluated with The Western Ontario and McMaster Universities Osteoarthritis score (WOMAC)...
December 7, 2018: Irish Journal of Medical Science
Yasuo Tanaka, Ryosuke Tateishi, Kazuhiko Koike
Proteoglycans, which consist of a protein core and glycosaminoglycan chains, are major components of the extracellular matrix and play physiological roles in maintaining tissue homeostasis. In the carcinogenic tissue microenvironment, proteoglycan expression changes dramatically. Altered proteoglycan expression on tumor and stromal cells affects cancer cell signaling pathways, which alters growth, migration, and angiogenesis and could facilitate tumorigenesis. This dysregulation of proteoglycans has been implicated in the pathogenesis of diseases such as hepatocellular carcinoma (HCC) and the underlying mechanism has been studied extensively...
October 8, 2018: International Journal of Molecular Sciences
Yang Xu, Jie Xu, Yanfang Yang, Lei Zhu, Xubin Li, Weipeng Zhao
BACKGROUND/AIMS: The chondroitin sulfate proteoglycan serglycin (SRGN), a hematopoietic cell granule proteoglycan, has been implicated in promoting tumor metastasis; however, the underlying mechanisms remain to be elucidated. The present study aimed to investigate the SRGN gene expression and its regulation as downstream signaling of hypoxia-inducible transcription factor 1 alpha (HIF-1α) in colorectal cancer (CRC) cells and tissues. METHODS: The expression of SRGN was analyzed in CRC specimens for its correlation with progression and metastasis...
2018: Cellular Physiology and Biochemistry
Jun Mei Hu Frisk, Lena Kjellén, Fabio R Melo, Helena Öhrvik, Gunnar Pejler
Mast cells (MCs) are characterized by an abundance of lysosome-like secretory granules filled with immunomodulatory compounds including histamine, cytokines, lysosomal hydrolases, MC-restricted proteases, and serglycin proteoglycans. The latter are essential for promoting the storage of other granule compounds and are built up of the serglycin core protein to which highly sulfated and thereby negatively charged glycosaminoglycan (GAG) side chains of heparin or chondroitin sulfate type are attached. In the search for mechanisms operating in regulating MC granule homeostasis, we here investigated the role of mitogen-activated protein kinase (MAPK) signaling...
2018: Frontiers in Immunology
Issan Yee San Tam, Chun Wai Ng, Hang Yung Alaster Lau, See-Ying Tam
BACKGROUND: Mast cells are key immune effector cells which release chemokines, proteases, and other inflammatory mediators upon activation by immunological stimuli. The aim of this study was to investigate the effects of co-releasing proteases on the kinetics of release of the chemokine monocyte chemoattractant protein-1 (MCP-1) in immunoglobulin E (IgE)-mediated activation of human mast cells. METHODS: Homogenous populations of mature and functional primary human mast cells were generated from CD34+ progenitors originated from buffy coats of healthy adult donors...
2018: International Archives of Allergy and Immunology
Panagiotis Bouris, Dimitra Manou, Anastasia Sopaki-Valalaki, Anthi Kolokotroni, Aristidis Moustakas, Aastha Kapoor, Renato V Iozzo, Nikos K Karamanos, Achilleas D Theocharis
Serglycin is an intracellular proteoglycan that is expressed and constitutively secreted by numerous malignant cells, especially prominent in the highly-invasive, triple-negative MDA-MB-231 breast carcinoma cells. Notably, de novo expression of serglycin in low aggressive estrogen receptor α (ERα)-positive MCF7 breast cancer cells promotes an aggressive phenotype. In this study, we discovered that serglycin promoted epithelial to mesenchymal transition (EMT) in MCF7 cells as shown by increased expression of mesenchymal markers vimentin, fibronectin and EMT-related transcription factor Snail2...
May 26, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Kouki Matsuo, Go Atsumi
Through the years, the post-translational modification of plant-made recombinant proteins has been a considerable problem. Protein glycosylation is arguably the most important post-translational modification; thus, for the humanization of protein glycosylation in plants, the introduction, repression, and knockout of many glycosylation-related genes has been carried out. In addition, plants lack mammalian-type protein O-glycosylation pathways; thus, for the synthesis of mammalian O-glycans in plants, the construction of these pathways is necessary...
September 2018: Journal of Bioscience and Bioengineering
Angela D'Ascola, Michele Scuruchi, Angela Avenoso, Giuseppe Bruschetta, Salvatore Campo, Giuseppe Mandraffino, Giuseppe M Campo
Serglycin is expressed by a variety of cell types and mediates different functions in both normal and pathological conditions by interacting with different biological molecules, such as the CD44 receptor. Many studies suggest that serglycin has a crucial role in inflammatory response, but there are limited data on the functions of this proteoglycan in chondrocytes. In this study we investigated the effect of serglycin knockdown induced by a specific serglycin small interfering RNA (SRGN siRNA) in normal mouse chondrocytes stimulated with lipopolysaccharide (LPS)...
May 15, 2018: Biochemical and Biophysical Research Communications
Vitor H Pomin, Barbara Mulloy
In this editorial to MDPI Pharmaceuticals special issue " Glycosaminoglycans and Proteoglycans " we describe in outline the common structural features of glycosaminoglycans and the characteristics of proteoglycans, including the intracellular proteoglycan, serglycin, cell-surface proteoglycans, like syndecans and glypicans, and the extracellular matrix proteoglycans, like aggrecan, perlecan, and small leucine-rich proteoglycans. The context in which the pharmaceutical uses of glycosaminoglycans and proteoglycans are presented in this special issue is given at the very end...
February 27, 2018: Pharmaceuticals
H E Gruber, E N Hanley
We investigated whether the multifunctional intercellular proteoglycan, serglycin, is expressed in human intervertebral disc cells and assessed its localization. We also investigated expression levels of serglycin in human annulus fibrosus (annulus) cells exposed to IL-1ß and TNF-α, which are two proinflammatory cytokines that are expressed during disc degeneration. Immunolocalization of serglycin was common in many cells of the human annulus, but less common in the nucleus pulposus (nucleus). Both intracellular and cell membrane localization were observed...
2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
Hasan Ata Bolayır, Tarık Kıvrak, Hakan Gunes, Aslı Bolayır, Ilgın Karaca
BACKGROUND: Serglycin plays a key role in the inflammatory status however the relationship between coronary artery disease (CAD) and serglycin is still unknown. AIM: In this study, we aimed to investigate association of serglycin levels with CAD severity in patients with stable angina pectoris (SAP). METHODS: In total, 100 SAP patients diagnosed by coronary angiography and clinical manifestations, and 100 control subjects matched for age and sex were enrolled in this case-control study...
2018: Kardiologia Polska
Jordan R Warford, Anna-Claire Lamport, Derek R Clements, Alicia Malone, Barry E Kennedy, Youra Kim, Shashi A Gujar, David W Hoskin, Alexander S Easton
Proteoglycans are promising therapeutic targets in Multiple Sclerosis (MS), because they regulate many aspects of the immune response. This was studied using surfen, an agent that binds both heparan sulphate proteoglycans (HSPGs) and chondroitin sulphate proteoglycans (CSPGs). Initial cell culture work on bone marrow derived macrophages (BMDMs) found that surfen reduced concentrations of the chemokines CCL2, CCL4 and CCL5, with reduced messenger (m)RNA expression for Tumor Necrosis Factor, IL-6, IL-1β and inducible nitric oxide synthase...
January 4, 2018: Acta Neuropathologica Communications
Rodrigo de Andrade Ferrazza, Henry David Mogollón Garcia, Elizabeth Moreira Dos Santos Schmidt, Monika Mihm Carmichael, Fabiana Ferreira de Souza, Richard Burchmore, Roberto Sartori, Peter David Eckersall, João Carlos Pinheiro Ferreira
Bovine follicular fluid (FF) constitutes the microenvironment of follicles and includes various biologically active proteins. We performed a study involving 18 healthy nonlactating Holstein cows to determine the protein expression profile of FF at key stages of follicular development. Follicles were individually aspirated in vivo at predeviation (F1 ∼ 7.0 mm), deviation (F1 ∼ 8.5 mm), postdeviation (F1 ∼ 12.0 mm), and preovulatory stages of follicle development, which were confirmed by measurement of follicular estradiol and progesterone concentrations...
January 1, 2017: Biology of Reproduction
Z Zhang, Y Deng, G Zheng, X Jia, Y Xiong, K Luo, Q Qiu, Ni Qiu, J Yin, M Lu, H Liu, Y Gu, Z He
Patients with triple-negative breast cancers (TNBC) are at a high risk for a recurrent or metastatic disease, and the molecular mechanisms associated with this risk are unclear. Proteoglycan serglycin (SRGN) proteins are involved in tumor metastasis, but their role in TNBC has not yet been elucidated. This study investigates the SRGN gene expression and how it regulates TGFβ2 and the downstream signaling of TGFβ2 in TNBC cells and tissues. Our results show that SRGN mRNA and protein expression levels were significantly higher in TNBC cell lines and tumor tissues than that in non-TNBC cells and tissues...
July 10, 2017: Oncogenesis
Harun Kundi, Murat Gök, Canan Topçuoglu, Ender Ornek
BACKGROUND: Serglycin plays an important role in the inflammatory status, but the relationship between coronary artery ectasia (CAE) and serglycin is still unknown. AIM: In this study, we aimed to investigate the association of serglycin level with isolated CAE. METHODS: Fifty-two patients with isolated CAE and 35 individuals with normal coronary angiography were included into the study. The Markis classification and number of ectatic coronary arteries were recorded...
2017: Kardiologia Polska
Ha Na Kim, John M Whitelock, Megan S Lord
Heparin and heparan sulfate are structurally-related carbohydrates with therapeutic applications in anticoagulation, drug delivery, and regenerative medicine. This study explored the effect of different bioreactor conditions on the production of heparin/heparan sulfate chains via the recombinant expression of serglycin in mammalian cells. Tissue culture flasks and continuously-stirred tank reactors promoted the production of serglycin decorated with heparin/heparan sulfate, as well as chondroitin sulfate, while the serglycin secreted by cells in the tissue culture flasks produced more highly-sulfated heparin/heparan sulfate chains...
May 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ananya Roy, Sanaz Attarha, Holger Weishaupt, Per-Henrik Edqvist, Fredrik J Swartling, Michael Bergqvist, Florian A Siebzehnrubl, Anja Smits, Fredrik Pontén, Elena Tchougounova
Serglycin is an intracellular proteoglycan with a unique ability to adopt highly divergent structures by glycosylation with variable types of glycosaminoglycans (GAGs) when expressed by different cell types. Serglycin is overexpressed in aggressive cancers suggesting its protumorigenic role. In this study, we explored the expression of serglycin in human glioma and its correlation with survival and immune cell infiltration. We demonstrate that serglycin is expressed in glioma and that increased expression predicts poor survival of patients...
April 11, 2017: Oncotarget
Megan S Lord, MoonSun Jung, John M Whitelock
Heparin has been used clinically as an anti-coagulant for more than 100 y and the major source of this therapeutic is still animal tissues. Contamination issues in some batches of heparin over 10 y ago have highlighted the need to develop alternative methods of production of this essential drug. 1 Bioengineering heparin by expressing serglycin in mammalian cells is a promising approach that was recently reported by the authors. 2 This addendum explores the approaches that the authors are taking to increase the yield of recombinantly expressed serglycin decorated with heparin/heparan sulfate focusing on cell culture and bioreactor conditions and proposes that the cell microenvironment is a key modulator of heparin biosynthesis...
September 3, 2017: Bioengineered
Richard L Stevens, H Patrick McNeil, Lislaine A Wensing, Kichul Shin, G William Wong, Philip M Hansbro, Steven A Krilis
The constitutive heparin+ (HP) mast cells (MCs) in mice express mouse MC protease (mMCP)-5 and carboxypeptidase A (mMC-CPA). The amino acid sequence of mMCP-5 is most similar to that of human chymase-1, as are the nucleotide sequences of their genes and transcripts. Using a homologous recombination approach, a C57BL/6 mouse line was created that possessed a disrupted mMCP-5 gene. The resulting mice were fertile and had no obvious developmental abnormality. Lack of mMCP-5 protein did not alter the granulation of the IL-3/IL-9-dependent mMCP-2+ MCs in the jejunal mucosa of Trichinella spiralis -infected mice...
March 31, 2017: Journal of Biological Chemistry
Luisa Lorenzi, Claudia Döring, Tobias Rausch, Vladimir Benes, Silvia Lonardi, Mattia Bugatti, Elias Campo, José Cabeçadas, Ingrid Simonitsch-Klupp, Anita Borges, Jay Mehta, Claudio Agostinelli, Stefano Aldo Pileri, Fabio Facchetti, Martin-Leo Hansmann, Sylvia Hartmann
Follicular dendritic cell (FDC)-sarcoma is a rare neoplasm with morphologic and phenotypic features of FDCs. It shows an extremely heterogeneous morphology, therefore, its diagnosis relys on the phenotype of tumor cells. Aim of the present study was the identification of new specific markers for FDC-sarcoma by whole transcriptome sequencing (WTS). Candidate markers were selected based on gene expression level and biological function. Immunohistochemistry was performed on reactive tonsils, on 22 cases of FDC-sarcomas and 214 control cases including 114 carcinomas, 87 soft tissue tumors, 5 melanomas, 5 thymomas and 3 interdigitating dendritic cell sarcomas...
March 7, 2017: Oncotarget
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