Milk fat globule epidermal growth factor‐8 limits tissue damage through inflammasome modulation during renal injury

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: MFG‐;    E8;    macrophage;    NLRP3;    unilateral ureteral obstruction;    fibrosis;   

DOI  :  10.1189/jlb.3A0515-213RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Mediatorsreleasedbyapoptoticrenalresidentcellsplayacrucialroleinmodificationoftheinflammatorymicroenvironment.Wehavedemonstratedthatmilkfatglobuleepidermalgrowthfactor8(MFG‐E8)isreleasedbyapoptoticcells,whichresultsinreducedproinflammatorycytokineproductionbymacrophages.ThepresentstudywasdesignedtostudytheroleofMFG‐E8onthemodulationoftissuedamageandmacrophagephenotypeinarenalinflammatorymodel,unilateralureteralobstruction(UUO).C57BL/6WTorMFG‐E8KOmiceunderwentureteralligationfor3,7,and14dtoevaluaterenalinjury.MFG‐E8(30µg/kg)orvehiclewasalsoadministeredi.p.MFG‐E8administrationreducedkidneydamageandfibrosiscomparedwithcontrol,whereasitsabsenceinMFG‐E8KOmicewasassociatedwithmoreseveredisease.Moreover,MFG‐E8administrationwasassociatedwithdecreasedinflammasomeactivationinthekidney.Furthermore,adoptivetransferofMFG‐E8–stimulatedmacrophagesreducedactivationofinflammasomeandtissuedamage.Inallcases,boththesystemicadministrationofMFG‐E8andMFG‐E8–treatedmacrophagespromotedaccumulationofanti‐inflammatoryCD206+macrophages.WeproposethattheprotectiveroleofMFG‐E8ismediatedthroughanti‐inflammatorymacrophagereprogrammingwhichresultsindecreasedinflammasomeactivation,preventingseveretissuedamage.ThesedataprovidevaluableinsightforidentificationofMFG‐E8asanoveltargetinmodulationofinflammatorydiseases...

【 授权许可】

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