A New C-Xyloside Induces Modifications of GAG Expression, Structure and Functional Properties 英文参考文献.docVIP

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A New C-Xyloside Induces Modifications of GAG Expression, Structure and Functional Properties 英文参考文献.doc

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A New C-Xyloside Induces Modifications of GAG Expression, Structure and Functional Properties 英文参考文献

ANewC-XylosideInducesModificationsofGAG Expression,StructureandFunctionalProperties EmilieVassal-Stermann1,AlbertDuranton2,AnnieF.Black2,GayaneAzadiguian2,JulienDemaude2, HuguesLortat-Jacob1,LionelBreton2.,RomainR.Vive`s1*. 1InstitutdeBiologieStructuraleJean-PierreEbel,Unite′ MixtedeRecherche(UMR)5075,CNRS-CEA-Universite′ JosephFourier,Grenoble,France,2L’Ore′alResearchand Innovation,Clichy,France Abstract Proteoglycans (PGs) are critically involved in major cellular processes. Most PG activities are due to the large interactive propertiesoftheirglycosaminoglycan(GAG)polysaccharidechains,whoseexpressionandfinestructuralfeaturesaretightly controlledbyacomplexandhighlyregulatedbiosynthesismachinery.XylosidesareknowntobypassPG-associatedGAG biosynthesisandprimetheassemblyoffreepolysaccharidechains.Theseare,therefore,attractivemoleculestointerfere withGAGexpressionandfunction.Recently,wehavedevelopedanewxylosidederivative,C-Xyloside,thatsharesclassical GAG-inducingxylosideactivitieswhileexhibitingimprovedmetabolicstability.WehavepreviouslyshownthatC-Xyloside had beneficial effects on skin homoeostasis/regeneration using a number of models, but its precise effects on GAG expressionandfinestructureremainedtobeaddressed.Inthisstudy,wehavethereforeinvestigatedthisindetails,usinga 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-XylosidealsoaffectedPG-borneGAGs,themaindifferencebeingobservedinCS/DS4-O/6-O- sulfation ratio. Such changes were found to affect the biological properties of CS/DS, as revealed by the significant reductioninbindingtoHepatocyteGrowthFactorobserveduponC-Xylosidetreatment.Overall,thisstudyprovidesnew insightsintotheeffe