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Matrix Biology : Journal of the... Mar 2015We provide a comprehensive classification of the proteoglycan gene families and respective protein cores. This updated nomenclature is based on three criteria: Cellular... (Review)
Review
We provide a comprehensive classification of the proteoglycan gene families and respective protein cores. This updated nomenclature is based on three criteria: Cellular and subcellular location, overall gene/protein homology, and the utilization of specific protein modules within their respective protein cores. These three signatures were utilized to design four major classes of proteoglycans with distinct forms and functions: the intracellular, cell-surface, pericellular and extracellular proteoglycans. The proposed nomenclature encompasses forty-three distinct proteoglycan-encoding genes and many alternatively-spliced variants. The biological functions of these four proteoglycan families are critically assessed in development, cancer and angiogenesis, and in various acquired and genetic diseases where their expression is aberrant.
Topics: Alternative Splicing; Animals; Extracellular Matrix; Humans; Multigene Family; Proteoglycans; Sequence Homology, Amino Acid
PubMed: 25701227
DOI: 10.1016/j.matbio.2015.02.003 -
Methods in Molecular Biology (Clifton,... 2022Chemical protein synthesis has achieved tremendous progress in the past decades. With the development of chemical ligation as powerful tools, the scope of synthetic...
Chemical protein synthesis has achieved tremendous progress in the past decades. With the development of chemical ligation as powerful tools, the scope of synthetic protein is greatly expanded. Proteoglycans are a class of sulfated glycoproteins widely distributed on the cell surface and in the extracellular matrix, which are extensively engaged in cellular communication events. Consisting of protein backbone and glycosaminoglycan(s) side chain, proteoglycans are highly complex and heterogeneous in nature. Chemical synthesis provides facile and reliable approach to these molecules, with defined glycan structure and sulfation pattern. One remaining problem is that the acid-labile sulfates could hardly survive during the typical solid phase peptide synthesis (SPPS) process. In this chapter, strategic design of a "glycopeptide cassette" for the preparation of sulfated glycoprotein is described. In particular, we provide protocols for the chemical synthesis of ectodomain fragment (23-120) of sulfated glycoprotein syndecan-1.
Topics: Glycopeptides; Glycosaminoglycans; Heparitin Sulfate; Polysaccharides; Proteoglycans; Sulfates
PubMed: 35761038
DOI: 10.1007/978-1-0716-2489-0_1 -
American Journal of Physiology. Renal... Aug 2016
Topics: Podocytes; Proteoglycans
PubMed: 27226109
DOI: 10.1152/ajprenal.00295.2016 -
American Journal of Physiology. Cell... Aug 2022Syndecan-1 (SDC-1) is a heparan sulfate (HS)/chondroitin sulfate proteoglycan (PG) of the cell surface and the extracellular matrix (ECM), which regulates a broad... (Review)
Review
Syndecan-1 (SDC-1) is a heparan sulfate (HS)/chondroitin sulfate proteoglycan (PG) of the cell surface and the extracellular matrix (ECM), which regulates a broad spectrum of physiological and pathological processes such as cell proliferation, migration, inflammation, matrix remodeling, wound healing, and tumorigenesis. Syndecan-1 represents the major PG of the liver, expressed by hepatocytes and cholangiocytes, and its elevated expression is a characteristic feature of liver diseases. The highest syndecan-1 expression is found in liver cirrhosis and in hepatocellular carcinoma (HCC) developed in cirrhotic livers. In addition, as being a hepatitis C receptor, hepatitis C virus (HCV)-infected livers produce extremely large amounts of syndecan-1. The serum levels of the cleaved (shedded) extracellular domain have clinical significance, as their increased concentration reflects on poor prognosis in cirrhosis as well as in cancer. In vivo experiments confirmed that syndecan-1 protects against early stages of fibrogenesis mainly by enhanced clearance of transforming growth factor β1 (TGFβ1) and thrombospondin-1 (THBS1) via circulation, and against hepatocarcinogenesis by interfering with several signaling pathways and enhancing cell cycle blockade. In addition, syndecan-1 is capable to hinder lipid metabolism and ribosomal biogenesis in induced cancer models. These observations together with its participation in the uptake of viruses (e.g., HCV and SARS-CoV-2) indicate that syndecan-1 is a central player in liver pathologies.
Topics: Carcinoma, Hepatocellular; Hepatitis C; Humans; Liver; Liver Neoplasms; Proteoglycans; Syndecan-1
PubMed: 35704700
DOI: 10.1152/ajpcell.00039.2022 -
International Journal of Molecular... Dec 2022Glucocorticoids are steroid hormones that play diverse roles in numerous normal and pathological processes. They are actively used to treat a wide variety of diseases,... (Review)
Review
Glucocorticoids are steroid hormones that play diverse roles in numerous normal and pathological processes. They are actively used to treat a wide variety of diseases, including neurodegenerative and inflammatory diseases, cancers, and COVID-19, among others. However, the long-term use of glucocorticoids is associated with numerous side effects. Molecular mechanisms of these negative side effects are not completely understood. Recently, arguments have been made that one such mechanisms may be related to the influence of glucocorticoids on O-glycosylated components of the cell surface and extracellular matrix, in particular on proteoglycans and glycosaminoglycans. The potential toxic effects of glucocorticoids on these glycosylated macromolecules are particularly meaningful for brain physiology because proteoglycans/glycosaminoglycans are the main extracellular components of brain tissue. Here, we aim to review the known effects of glucocorticoids on proteoglycan expression and glycosaminoglycan content in different tissues, with a specific focus on the brain.
Topics: Humans; Glucocorticoids; Glycosaminoglycans; Proteoglycans
PubMed: 36555315
DOI: 10.3390/ijms232415678 -
Biomolecules Nov 2022Tauopathies are a class of neurodegenerative diseases, including Alzheimer's disease, and are characterized by intraneuronal tau inclusion in the brain and the patient's... (Review)
Review
Tauopathies are a class of neurodegenerative diseases, including Alzheimer's disease, and are characterized by intraneuronal tau inclusion in the brain and the patient's cognitive decline with obscure pathogenesis. Heparan sulfate proteoglycans, a major type of extracellular matrix, have been believed to involve in tauopathies. The heparan sulfate proteoglycans co-deposit with tau in Alzheimer's patient brain, directly bind to tau and modulate tau secretion, internalization, and aggregation. This review summarizes the current understanding of the functions and the modulated molecular pathways of heparan sulfate proteoglycans in tauopathies, as well as the implication of dysregulated heparan sulfate proteoglycan expression in tau pathology and the potential of targeting heparan sulfate proteoglycan-tau interaction as a novel therapeutic option.
Topics: Humans; Alzheimer Disease; Extracellular Matrix; Heparan Sulfate Proteoglycans; Tauopathies
PubMed: 36551220
DOI: 10.3390/biom12121792 -
Glycoconjugate Journal Jun 2017Mast cells contain granules packed with a mixture of proteins that are released on degranulation. The proteoglycan serglycin carries an array of glycosaminoglycan (GAG)... (Review)
Review
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. Recent emphasis on the analysis of mast cell heparin from different species and tissues, arising from the use of this GAG in medicine, lead to the question of whether variations within heparin structures between mast cell populations are as significant as variations in the mix of chondroitins and heparins.
Topics: Animals; Carbohydrate Conformation; Carbohydrate Sequence; Cell Degranulation; Cells, Cultured; Chondroitin Sulfates; Cytoplasmic Granules; Dermatan Sulfate; Heparin; Humans; Mast Cells; Peptide Hydrolases; Protein Binding; Proteoglycans; Structure-Activity Relationship; Vesicular Transport Proteins
PubMed: 27900574
DOI: 10.1007/s10719-016-9749-0 -
Biomolecules Feb 2021Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection... (Review)
Review
Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes including cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particular, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells. In this review, we explore the role of syndecans in tumorigenesis as well as their potential as therapeutic targets. Finally, this work reviews the contribution of syndecan-1 and syndecan-2 in PDAC progression and illustrates its potential to be targeted in future treatments for this devastating disease.
Topics: Animals; Carcinoma, Pancreatic Ductal; Extracellular Matrix; Humans; Proteoglycans; Signal Transduction; Syndecans
PubMed: 33669066
DOI: 10.3390/biom11030349 -
Pflugers Archiv : European Journal of... Oct 2022Proinflammatory cytokines target vascular endothelial cells during COVID-19 infections. In particular, the endothelial glycocalyx (eGC), a proteoglycan-rich layer on top... (Review)
Review
Proinflammatory cytokines target vascular endothelial cells during COVID-19 infections. In particular, the endothelial glycocalyx (eGC), a proteoglycan-rich layer on top of endothelial cells, was identified as a vulnerable, vasoprotective structure during infections. Thus, eGC damage can be seen as a hallmark in the development of endothelial dysfunction and inflammatory processes. Using sera derived from patients suffering from COVID-19, we could demonstrate that the eGC became progressively worse in relation to disease severity (mild vs severe course) and in correlation to IL-6 levels. This could be prevented by administering low doses of spironolactone, a well-known and highly specific aldosterone receptor antagonist. Our results confirm that SARS-CoV-2 infections cause eGC damage and endothelial dysfunction and we outline the underlying mechanisms and suggest potential therapeutic options.
Topics: COVID-19; Cytokines; Endothelial Cells; Glycocalyx; Humans; Interleukin-6; Mineralocorticoid Receptor Antagonists; Proteoglycans; SARS-CoV-2; Spironolactone; COVID-19 Drug Treatment
PubMed: 35867189
DOI: 10.1007/s00424-022-02726-3 -
American Journal of Physiology. Cell... Jun 2022Rheumatoid arthritis (RA) is a common autoimmune disease that causes inflammation of the joints and damage to the cartilage and bone. The pathogenesis of RA is... (Review)
Review
Rheumatoid arthritis (RA) is a common autoimmune disease that causes inflammation of the joints and damage to the cartilage and bone. The pathogenesis of RA is characterized in many patients by the presence of antibodies against citrullinated proteins. Proteoglycans are key structural elements of extracellular matrix in the joint articular cartilage and synovium and are secreted as lubricants in the synovial fluid. Alterations of proteoglycans contribute to RA pathogenesis. Proteoglycans such as aggrecan can be citrullinated and become potential targets of the rheumatoid autoimmune response. Proteoglycans are also upregulated in RA joints and/or undergo alterations of their regulatory functions over cytokines and chemokines, which promotes inflammation and bone damage. Recent studies have aimed to not only clarify these mechanisms but also develop novel proteoglycan-modulating therapeutics. These include agents altering the function and signaling of proteoglycans as well as tolerizing agents targeting citrullinated aggrecan. This mini-review summarizes the most recent findings regarding the dysregulation of proteoglycans that contributes to RA pathogenesis and the potential for proteoglycan-modulating agents to improve upon current RA therapy.
Topics: Aggrecans; Arthritis, Rheumatoid; Humans; Inflammation; Proteoglycans; Synovial Fluid
PubMed: 35476502
DOI: 10.1152/ajpcell.00086.2022