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[目的]探讨miR-21／FZD6轴在香烟浸提物(cigarettesmokeextract,CSE)促进肺支气管上皮细胞胞外基质(extraceLLuLarmatrix,ECM)重塑中的功能及作用机制.[方法]CSE处理肺支气管上皮细胞16HBE后,检测 WNT通路和ECM重构相关基因的表达;筛选可靶向 WNT通路的 miRNA,并验证;干扰miR-21表达,westernbLot检测FZD6表达变化,双荧光素酶实验验证miR-21与FZD6的靶向关系;回复实验验证该通路在CSE促进ECM重塑中的功能与作用.[结果]CSE处理可抑制WNT通路活性和ECM重塑相关基因的表达;miRNA筛选及细胞验证后得到 miR-21-5p和FZD6;CSE处理后,miR-21-5p表达上调,而FZD6的表达下调;干扰miR-21-5p可增强FZD6的表达,双荧光素酶实验表明 miR-21-5p可靶向FZD6.回复实验验证结果显示si-FZD6可促进ECM重塑相关基因表达;miR-21inhibitor可抑制ECM重塑相关基因表达,并可部分逆转si-FZD6对ECM重塑的促进效果.[结论]CSE可诱导肺支气管上皮细胞中 miR-21-5p的表达,削弱FZD6的表达,进而抑制 WNT通路的活性,加速肺支气管上皮细胞ECM重塑进程.“,”[Objective]Toinvestigatethefunctionand mechanism ofmiR-21／FZD6axisinextraceLLuLar matrix(ECM)remodeLingofLungbronchiaLepitheLiaLceLLsinducedbycigarettesmokeextracts(CSE).[Meth-ods]After16HBEwastreatedwithCSE,theexpressionofWNTpathwayandECMremodeLingreLatedgenes weredetected,andmiRNA,targetingWNTpathwaywasscreenedandverified.AfterinterferingwithmiR-21 expression,theexpressionofFZD6wasdetectedbywesternbLot,andthetargetreLationshipbetweenmiR-21 andFZD6wasverifiedbydoubLeLuciferaseassay.ThefunctionofthepathwayinpromotingECMremodeLing byCSEwereverifiedbyresponseexperiment.[ResuLts]CSEtreatmentcouLdinhibittheactivityofWNTpath-wayandtheexpressionofECMremodeLing-reLatedgenes;microRNAsscreeningandceLLvaLidationresuLtedin theexpressionofmicroRNAs-21-5pandFZD6;afterCSEtreatment,theexpressionofmicroRNAs-21-5pwas up-reguLated,whiLetheexpressionofFZD6wasdown-reguLated;interferingwithmicroRNAs-21-5pcouLden-hancetheexpressionofFZD6;doubLeLuciferaseassayshowedthatmicroRNAs-21-5pcouLdtargetFZD6.The resuLtsofresponseexperimentsshowedthatsi-FZD6couLdpromotetheexpressionofgenesreLatedtoECMre-modeLing,andthatmiR-21inhibitorcouLdinhibittheexpressionofgenesreLatedtoECMremodeLingandpart-Lyreversetheeffectofsi-FZD6onECMremodeLing.[ConcLusion]CSEcaninducetheexpressionofmicroRNA-21-5pinLungbronchiaLepitheLiaLceLLs,weakentheexpressionofFZD6,inhibittheactivityofWNTpathway, andacceLeratetheprocessofECMremodeLinginLungbronchiaLepitheLiaLceLLs.