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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...
April 12, 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
Megan S Lord, Bill Cheng, Brooke L Farrugia, Simon McCarthy, John M Whitelock
Platelet factor 4 (PF4) is produced by platelets with roles in both inflammation and wound healing. PF4 is stored in platelet α-granules bound to the glycosaminoglycan (GAG) chains of serglycin. This study revealed that platelet serglycin is decorated with chondroitin/dermatan sulfate and that PF4 binds to these GAG chains. Additionally, PF4 had a higher affinity for endothelial-derived perlecan heparan sulfate chains than serglycin GAG chains. The binding of PF4 to perlecan was found to inhibit both FGF2 signaling and platelet activation...
March 10, 2017: Journal of Biological Chemistry
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...
June 2017: Glycoconjugate Journal
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...
April 27, 2017: Oncogene
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
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...
November 2016: Metabolic Engineering
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