Disease-specific glycosaminoglycan patterns in the extracellular matrix of human lung and brain

Ennemoser, Maria; Pum, Alexandra; Kungl, Andreas J.

doi:10.1016/j.carres.2021.108480

Cited by 6 publications

(3 citation statements)

References 156 publications

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“…GAGs/PGs, as the main component of ECM, are involved in the development and progression of almost all human diseases. Pulmonary diseases have a high morbidity and mortality, such as pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease (COPD) [245,246]. In idiopathic pulmonary fibrosis, CS/DS, HA, and the CS/DS ratio increased significantly.…”

Section: Gags In Other Diseasesmentioning

confidence: 99%

The Alterations and Roles of Glycosaminoglycans in Human Diseases

Wang

2022

Polymers

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Glycosaminoglycans (GAGs) are a heterogeneous family of linear polysaccharides which are composed of a repeating disaccharide unit. They are also linked to core proteins to form proteoglycans (PGs). GAGs/PGs are major components of the cell surface and the extracellular matrix (ECM), and they display critical roles in development, normal function, and damage response in the body. Some properties (such as expression quantity, molecular weight, and sulfation pattern) of GAGs may be altered under pathological conditions. Due to the close connection between these properties and the function of GAGs/PGs, the alterations are often associated with enormous changes in the physiological/pathological status of cells and organs. Therefore, these GAGs/PGs may serve as marker molecules of disease. This review aimed to investigate the structural alterations and roles of GAGs/PGs in a range of diseases, such as atherosclerosis, cancer, diabetes, neurodegenerative disease, and virus infection. It is hoped to provide a reference for disease diagnosis, monitoring, prognosis, and drug development.

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Section: Gags In Other Diseasesmentioning

confidence: 99%

The Alterations and Roles of Glycosaminoglycans in Human Diseases

Wang

2022

Polymers

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“…A characteristic feature of the brain ECM is that it consists mainly of glycosylated macromolecules, such as proteoglycans (PGs), which play a critical role in brain physiology and cancer development [ 11 , 12 , 13 ]. The polysaccharide chains of PGs called glycosaminoglycans (GAGs) make a significant contribution to the functional activity of PGs and alterations of their composition/structure are often associated with various pathological conditions [ 14 , 15 , 16 ]. The important role of GAG in the development and pathological conditions of the nervous system is presented in the reviews [ 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone Inhibits Heparan Sulfate Biosynthetic System and Decreases Heparan Sulfate Content in Orthotopic Glioblastoma Tumors in Mice

Sokolov

Shevelev

Khotskina

et al. 2023

IJMS

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Glioblastoma (GB) is an aggressive cancer with a high probability of recurrence, despite active chemoradiotherapy with temozolomide (TMZ) and dexamethasone (DXM). These systemic drugs affect the glycosylated components of brain tissue involved in GB development; however, their effects on heparan sulfate (HS) remain unknown. Here, we used an animal model of GB relapse in which SCID mice first received TMZ and/or DXM (simulating postoperative treatment) with a subsequent inoculation of U87 human GB cells. Control, peritumor and U87 xenograft tissues were investigated for HS content, HS biosynthetic system and glucocorticoid receptor (GR, Nr3c1). In normal and peritumor brain tissues, TMZ/DXM administration decreased HS content (5–6-fold) but did not affect HS biosynthetic system or GR expression. However, the xenograft GB tumors grown in the pre-treated animals demonstrated a number of molecular changes, despite the fact that they were not directly exposed to TMZ/DXM. The tumors from DXM pre-treated animals possessed decreased HS content (1.5–2-fold), the inhibition of HS biosynthetic system mainly due to the -3–3.5-fold down-regulation of N-deacetylase/N-sulfotransferases (Ndst1 and Ndst2) and sulfatase 2 (Sulf2) expression and a tendency toward a decreased expression of the GRalpha but not the GRbeta isoform. The GRalpha expression levels in tumors from DXM or TMZ pre-treated mice were positively correlated with the expression of a number of HS biosynthesis-involved genes (Ext1/2, Ndst1/2, Glce, Hs2st1, Hs6st1/2), unlike tumors that have grown in intact SCID mice. The obtained data show that DXM affects HS content in mouse brain tissues, and GB xenografts grown in DXM pre-treated animals demonstrate attenuated HS biosynthesis and decreased HS content.

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“…For internalisation of tau, which is involved in the prion-like spread of tau pathology, 6-O and 3-O sulphation is a driver ( Rauch et al, 2018 ), with syndecan the probable core protein. High expression of the enzyme that mediates 3-O sulphation, 3-O HS sulphotransferase (Hs3st1), is a risk factor for Alzheimer’s disease ( Ennemoser et al, 2022 ). HSPGs are also involved in the clearance of amyloid from the brain ( Morawski et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Proteoglycan Sulphation in the Function of the Mature Central Nervous System

Fawcett

Kwok

2022

Front. Integr. Neurosci.

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Chondroitin sulphate and heparan sulphate proteoglycans (CSPGS and HSPGs) are found throughout the central nervous system (CNS). CSPGs are ubiquitous in the diffuse extracellular matrix (ECM) between cells and are a major component of perineuronal nets (PNNs), the condensed ECM present around some neurons. HSPGs are more associated with the surface of neurons and glia, with synapses and in the PNNs. Both CSPGs and HSPGs consist of a protein core to which are attached repeating disaccharide chains modified by sulphation at various positions. The sequence of sulphation gives the chains a unique structure and local charge density. These sulphation codes govern the binding properties and biological effects of the proteoglycans. CSPGs are sulphated along their length, the main forms being 6- and 4-sulphated. In general, the chondroitin 4-sulphates are inhibitory to cell attachment and migration, while chondroitin 6-sulphates are more permissive. HSPGs tend to be sulphated in isolated motifs with un-sulphated regions in between. The sulphation patterns of HS motifs and of CS glycan chains govern their binding to the PTPsigma receptor and binding of many effector molecules to the proteoglycans, such as growth factors, morphogens, and molecules involved in neurodegenerative disease. Sulphation patterns change as a result of injury, inflammation and ageing. For CSPGs, attention has focussed on PNNs and their role in the control of plasticity and memory, and on the soluble CSPGs upregulated in glial scar tissue that can inhibit axon regeneration. HSPGs have key roles in development, regulating cell migration and axon growth. In the adult CNS, they have been associated with tau aggregation and amyloid-beta processing, synaptogenesis, growth factor signalling and as a component of the stem cell niche. These functions of CSPGs and HSPGs are strongly influenced by the pattern of sulphation of the glycan chains, the sulphation code. This review focuses on these sulphation patterns and their effects on the function of the mature CNS.

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Disease-specific glycosaminoglycan patterns in the extracellular matrix of human lung and brain

Cited by 6 publications

References 156 publications

The Alterations and Roles of Glycosaminoglycans in Human Diseases

The Alterations and Roles of Glycosaminoglycans in Human Diseases

Dexamethasone Inhibits Heparan Sulfate Biosynthetic System and Decreases Heparan Sulfate Content in Orthotopic Glioblastoma Tumors in Mice

Proteoglycan Sulphation in the Function of the Mature Central Nervous System

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