Sequence features, structure, ligand interaction, and diseases in small leucine rich repeat proteoglycans

Matsushima, Norio; Miyashita, Hiroki; Kretsinger, Robert H.

doi:10.1007/s12079-021-00616-4

Cited by 20 publications

(21 citation statements)

References 120 publications

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“…AF falls into internal and external parts, which include 15–25 layers of highly packed inclined collagen fiber lamellas and interspersed proteoglycans ( Matsushima et al, 2021 ). The lamellas cross each other, and adjacent layers are reversed.…”

Section: Intervertebral Disc and Intervertebral Disc Degenerationmentioning

confidence: 99%

Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration

Wu²,

Tan

et al. 2022

Front. Pharmacol.

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Low back pain has been found as a major cause of global disease burden and disability. Intervertebral disc degeneration is recognized as the vital factor causing low back pain. Intervertebral disc degeneration has a complex mechanism and cannot be avoided. Traditional strategies for the treatment of intervertebral disc degeneration cannot meet the needs of intervertebral disc regeneration, so novel treatment methods are urgently required. Exosomes refer to extracellular vesicles that can be released by most cells, and play major roles in intercellular material transport and information transmission. MicroRNAs have been identified as essential components in exosomes, which can be selectively ingested by exosomes and delivered to receptor cells for the regulation of the physiological activities and functions of receptor cells. Existing studies have progressively focused on the role of exosomes and exosomal microRNAs in the treatment of intervertebral disc degeneration. The focus on this paper is placed on the changes of microenvironment during intervertebral disc degeneration and the biogenesis and mechanism of action of exosomes and exosomal microRNAs. The research results and deficiencies of exosomes and exosomal microRNAs in the regulation of apoptosis, extracellular matrix homeostasis, inflammatory response, oxidative stress, and angiogenesis in intervertebral disc degeneration are primarily investigated. The aim of this paper is to identify the latest research results, potential applications and challenges of this emerging treatment strategy.

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Section: Intervertebral Disc and Intervertebral Disc Degenerationmentioning

confidence: 99%

Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration

Wu²,

Tan

et al. 2022

Front. Pharmacol.

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“…They are composed of a relatively small protein core of about 40-60 kDa that contains 10-12 motifs of leucine-rich repeats (LRRs) and is flanked by characteristic cysteine-rich clusters with defined spacing. Additionally, the heterogeneous GAG chains are post-translationally attached to the protein core (85,(90)(91)(92). To date, there are 18 known SLRPs, which are classified into five distinct classes, based on their Nterminal cysteine-rich clusters, evolutionary conservation, sequence homology, and GAG chains (85).…”

Section: Structural Characteristics Of Small Leucine-rich Proteoglycansmentioning

confidence: 99%

“…To date, there are 18 known SLRPs, which are classified into five distinct classes, based on their N-terminal cysteine-rich clusters, evolutionary conservation, sequence homology, and GAG chains ( 85 ). The LRRs of the protein core, which give rise to the characteristic solenoid structure of SLRPs, contain a conserved hydrophobic motif wherein distinct leucines can be substituted by other hydrophobic amino acids ( 90 ). Irrespective of their classification, all SLRPs share common biological functions, and most importantly, their capability to interact with various cell surface receptors such as receptor tyrosine kinases (RTKs) and TLRs, thus mediating divers downstream signaling events that regulate vital cellular pathways and processes that are also implicated in cancer, including inflammation and autophagy ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of Decorin and Biglycan Signaling in Tumorigenesis

Diehl

Huber²,

Trebicka³

et al. 2021

Front. Oncol.

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The complex and adaptive nature of malignant neoplasm constitute a major challenge for the development of effective anti-oncogenic therapies. Emerging evidence has uncovered the pivotal functions exerted by the small leucine-rich proteoglycans, decorin and biglycan, in affecting tumor growth and progression. In their soluble forms, decorin and biglycan act as powerful signaling molecules. By receptor-mediated signal transduction, both proteoglycans modulate key processes vital for tumor initiation and progression, such as autophagy, inflammation, cell-cycle, apoptosis, and angiogenesis. Despite of their structural homology, these two proteoglycans interact with distinct cell surface receptors and thus modulate distinct signaling pathways that ultimately affect cancer development. In this review, we summarize growing evidence for the complex roles of decorin and biglycan signaling in tumor biology and address potential novel therapeutic implications.

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“…The (SLRP) family ( 203 ) includes decorin, biglycan and lumican all produced by EC, including glomerular EC in culture ( 164 ) and in vivo ( 204 , 205 ). These SLRPs are characterized by a small core protein (~ 40 kDa) with few CS/DS or KS GAG chains ( 206 ).…”

Section: Molecular Components Of the Ec Glycocalyxmentioning

confidence: 99%

“…Lumican is found in a high-salt eluate of renal vessels ( 115 , 208 ), suggesting that it is a major component of the ESL. The SLRPs interact with, and regulate the function of TGF-β and its family members and other growth factors ( 203 ). Most recently decorin was shown to activate the autophagy pathway in EC ( 209 ).…”

Section: Molecular Components Of the Ec Glycocalyxmentioning

confidence: 99%

The Glomerular Endothelium Restricts Albumin Filtration

2021

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Inflammatory activation and/or dysfunction of the glomerular endothelium triggers proteinuria in many systemic and localized vascular disorders. Among them are the thrombotic microangiopathies, many forms of glomerulonephritis, and acute inflammatory episodes like sepsis and COVID-19 illness. Another example is the chronic endothelial dysfunction that develops in cardiovascular disease and in metabolic disorders like diabetes. While the glomerular endothelium is a porous sieve that filters prodigious amounts of water and small solutes, it also bars the bulk of albumin and large plasma proteins from passing into the glomerular filtrate. This endothelial barrier function is ascribed predominantly to the endothelial glycocalyx with its endothelial surface layer, that together form a relatively thick, mucinous coat composed of glycosaminoglycans, proteoglycans, glycolipids, sialomucins and other glycoproteins, as well as secreted and circulating proteins. The glycocalyx/endothelial surface layer not only covers the glomerular endothelium; it extends into the endothelial fenestrae. Some glycocalyx components span or are attached to the apical endothelial cell plasma membrane and form the formal glycocalyx. Other components, including small proteoglycans and circulating proteins like albumin and orosomucoid, form the endothelial surface layer and are bound to the glycocalyx due to weak intermolecular interactions. Indeed, bound plasma albumin is a major constituent of the endothelial surface layer and contributes to its barrier function. A role for glomerular endothelial cells in the barrier of the glomerular capillary wall to protein filtration has been demonstrated by many elegant studies. However, it can only be fully understood in the context of other components, including the glomerular basement membrane, the podocytes and reabsorption of proteins by tubule epithelial cells. Discovery of the precise mechanisms that lead to glycocalyx/endothelial surface layer disruption within glomerular capillaries will hopefully lead to pharmacological interventions that specifically target this important structure.

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Sequence features, structure, ligand interaction, and diseases in small leucine rich repeat proteoglycans

Cited by 20 publications

References 120 publications

Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration

Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration

The Role of Decorin and Biglycan Signaling in Tumorigenesis

The Glomerular Endothelium Restricts Albumin Filtration

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