Anti-Bacterial Effects of Poly-N-Acetyl-Glucosamine Nanofibers in Cutaneous Wound Healing Requirement for Akt1 英文参考文献.docVIP

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Anti-Bacterial Effects of Poly-N-Acetyl-Glucosamine Nanofibers in Cutaneous Wound Healing Requirement for Akt1 英文参考文献.doc

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Anti-Bacterial Effects of Poly-N-Acetyl-Glucosamine Nanofibers in Cutaneous Wound Healing Requirement for Akt1 英文参考文献

Anti-BacterialEffectsofPoly-N-Acetyl-Glucosamine NanofibersinCutaneousWoundHealing:Requirement forAkt1 HaleyBuffLindner1,AiguoZhang3,JuanitaEldridge1,MarinaDemcheva2,PhilipTsichilis4,ArunSeth3, JohnVournakis2,RobinC.Muise-Helmericks1* 1DepartmentofRegenerativeMedicineandCellBiology,MedicalUniversityofSouthCarolina,Charleston,SouthCarolina,UnitedStatesofAmerica,2MarinePolymer Technologies,Danvers,Massachusetts,UnitedStatesofAmerica,3SunnybrookResearchInstitute,UniversityofToronto,Toronto,Ontario,Canada,4MolecularOncology ResearchInstitute,TuftsUniversity,Medford,Massachusetts,UnitedStatesofAmerica Abstract Background: Treatment of cutaneous wounds with poly-N-acetyl-glucosamine nanofibers (sNAG) results in increased kinetics of wound closure in diabetic animal models, which is due in part to increased expression of several cytokines, growthfactors,andinnateimmuneactivation.Defensinsarealsoimportantforwoundhealingandanti-microbialactivities. Therefore,wetestedwhethersNAGnanofibersinducedefensinexpressionresultinginbacterialclearance. Methodology: The role of sNAG in defensin expression was examined using immunofluoresence microscopy, pharmacologicalinhibition,andshRNAknockdowninvitro.TheabilityofsNAGtreatmenttoinducedefensinexpression andbacterialclearance in WTandAKT12/2 mice wascarried outusing immunofluoresentmicroscopy andtissuegram staining. Neutralization, using an antibody directed against b-defensin 3, was utilized to determine if the antimicrobial propertiesofsNAGaredependentontheinductionofdefensinexpression. Conclusions/Findings:sNAGtreatmentcausesincreasedexpressionofbotha-andb-typedefensinsinendothelialcellsand b-typedefensinsinkeratinocytes.PharmacologicalinhibitionandshRNAknockdownimplicatesAkt1insNAG-dependent defensinexpressioninvitro,anactivityalsoshowninaninvivowoundhealingmodel.Importantly,sNAGtreatmentresults in increased kinetics of wound closure in wild type animals. sNAG treatment decreases bacterial infection of cutaneous wounds infected