Modifications of proteoglycans secreted into the growth medium by young and senescent human skin fibroblasts

Passi, Alberto; Albertini, Riccardo; Campagnari, Francesco; Luca, Giancarlo De

doi:10.1016/s0014-5793(97)00008-2

Cited by 21 publications

(17 citation statements)

References 30 publications

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“…The consequences of skin ageing on GAGs remain poorly understood. However, increasing evidence suggest that age-related alteration of the dermal connective tissue may involve a remodeling of GAG expression and structure [32], [33], [34]. In addition, a recent publication reports that senescence of dermal stem cells occurs during the aging process and affects their functions [35], highlighting the need to investigate the possible connection between GAGs, stem cells and aging in the near future.…”

Section: Discussionmentioning

confidence: 99%

A New C-Xyloside Induces Modifications of GAG Expression, Structure and Functional Properties

et al. 2012

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Proteoglycans (PGs) are critically involved in major cellular processes. Most PG activities are due to the large interactive properties of their glycosaminoglycan (GAG) polysaccharide chains, whose expression and fine structural features are tightly controlled by a complex and highly regulated biosynthesis machinery. Xylosides are known to bypass PG-associated GAG biosynthesis and prime the assembly of free polysaccharide chains. These are, therefore, attractive molecules to interfere with GAG expression and function. Recently, we have developed a new xyloside derivative, C-Xyloside, that shares classical GAG-inducing xyloside activities while exhibiting improved metabolic stability. We have previously shown that C-Xyloside had beneficial effects on skin homoeostasis/regeneration using a number of models, but its precise effects on GAG expression and fine structure remained to be addressed. In this study, we have therefore investigated this in details, using a reconstructed dermal tissue as model. Our results first confirmed that C-Xyloside strongly enhanced synthesis of GAG chains, but also induced significant changes in their structure. C-Xyloside primed GAGs were exclusively chondroitin/dermatan sulfate (CS/DS) that featured reduced chain size, increased O-sulfation, and changes in iduronate content and distribution. Surprisingly, C-Xyloside also affected PG-borne GAGs, the main difference being observed in CS/DS 4-O/6-O-sulfation ratio. Such changes were found to affect the biological properties of CS/DS, as revealed by the significant reduction in binding to Hepatocyte Growth Factor observed upon C-Xyloside treatment. Overall, this study provides new insights into the effect of C-Xyloside on GAG structure and activities, which opens up perspectives and applications of such compound in skin repair/regeneration. It also provides a new illustration about the use of xylosides as tools for modifying GAG fine structure/function relationships.

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Section: Discussionmentioning

confidence: 99%

A New C-Xyloside Induces Modifications of GAG Expression, Structure and Functional Properties

et al. 2012

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“…In particular, the proportions of collagen, elastin, and glycosaminoglycans alter in a manner reminiscent of changes in extracellular matrix production seen between senescent and growing fibroblasts in vitro. (50,51) This coupled with the direct observation of senescent fibroblasts in the ageing dermis (30) strongly suggests that the tissue balance in aged skin is altered towards a more catabolic state.…”

Section: Potential Impact Of Cellular Senescence On Human Tissuesmentioning

confidence: 99%

How might replicative senescence contribute to human ageing?

1999

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“…We have previously shown that hyaluronic acid secreted by human lung VSMC (Papakonstantinou et al, 1995) acts as a negative regulator for VSMC proliferation and as a positive regulator for VSMC migration (Papakonstantinou et al, 1998a). Similarly, dermatan sulfate has been correlated with lowered rates of cell proliferation and cellular senescence (Passi et al, 1997). Heparin also exhibits antiproliferative activity on VSMC, suppresses vascular remodeling, and reduces the development of pulmonary hypertension in vivo (Thompson et al, 1994).…”

Section: Hypoxia Modifies Glycosaminoglycan Synthesis 835mentioning

confidence: 99%

“…Heparin also exhibits antiproliferative activity on VSMC, suppresses vascular remodeling, and reduces the development of pulmonary hypertension in vivo (Thompson et al, 1994). Thus, it is possible that the deposition of molecules that inhibit lung cell proliferation, such as hyaluronic acid (Papakonstantinou et al, 1998a), dermatan sulfate (Passi et al, 1997), or heparin (Sasaki et al, 2000), may represent an autoregulatory mechanism by which lung cells counteract the effects of mitogenic stimuli associated with lung fibrosis (Moseley et al, 1986).…”

Section: Hypoxia Modifies Glycosaminoglycan Synthesis 835mentioning

confidence: 99%

Hypoxia Differentially Enhances the Effects of Transforming Growth Factor-β Isoforms on the Synthesis and Secretion of Glycosaminoglycans by Human Lung Fibroblasts

Papakonstantinou

Roth²,

Tamm³

et al. 2002

J Pharmacol Exp Ther

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Interstitial lung diseases associated with hypoxia, such as lung fibrosis, are characterized by enhanced production of transforming growth factor-␤ (TGF-␤) and increased deposition of extracellular matrix (ECM) molecules, including glycosaminoglycans (GAGs). In this study, we investigated the effect of hypoxia (3% O 2 ) on TGF-␤-induced GAG synthesis by primary human pulmonary fibroblasts, established from lung biopsies. Total GAG synthesis was assessed by the incorporation of [ 3 H]glucosamine into GAGs associated with the cell layer (cells and ECM) or secreted in the medium. GAGs were isolated and purified by gel filtration, fractionated by electrophoresis on cellulose acetate membranes, and characterized using GAGdegrading enzymes. GAG molecules identified in the cell layer and the medium were: hyaluronic acid, and chondroitin, dermatan, and heparan sulfates. All TGF-␤ isoforms time dependently induced [3 H]glucosamine incorporation into GAGs of the cell layer or the medium. Characterization of individual GAG molecules indicated that this was attributed to dermatan and heparan sulfates in the cell layer and to hyaluronic acid and chondroitin and dermatan sulfates in the medium. Hypoxia enhanced the effect of all TGF-␤ isoforms, particularly that of TGF-␤3, on the secretion of hyaluronic acid and chondroitin and dermatan sulfates. In the cell layer, hypoxia stimulated only the effect of TGF-␤2-induced [ 3 H]glucosamine incorporation into GAGs. Our data indicate that hypoxia differentially enhances the effect of TGF-␤ isoforms on the secretion and deposition of GAGs and may hasten ECM remodeling associated with the pathogenesis of lung fibrosis.

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Modifications of proteoglycans secreted into the growth medium by young and senescent human skin fibroblasts

Cited by 21 publications

References 30 publications

A New C-Xyloside Induces Modifications of GAG Expression, Structure and Functional Properties

A New C-Xyloside Induces Modifications of GAG Expression, Structure and Functional Properties

How might replicative senescence contribute to human ageing?

Hypoxia Differentially Enhances the Effects of Transforming Growth Factor-β Isoforms on the Synthesis and Secretion of Glycosaminoglycans by Human Lung Fibroblasts

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