作者：陈子硕, 刘誉

作者单位：四川大学生命科学学院, 四川 成都 610064

关键词：1,25-二羟基维生素D₃;维生素D受体基因敲除鼠;基质金属蛋白酶7;α防御素

摘要：

为探索维生素D对肠道先天免疫抗菌肽-防御素1（alpha-1-defensin，DEFA1）剪切酶基质金属蛋白酶7（matrix metalloproteinase 7，MMP-7）的调控，利用维生素D受体基因敲除小鼠（Vitamin D receptor knock-out，VDR-KO）与肠道细胞系作为研究模型，通过免疫组化染色、qRT-PCR及免疫印迹等研究方法，发现其肠道细胞中MMP-7的转录水平与蛋白水平较野生型（wild type，WT）小鼠显著降低，并且DEFA1的表达量也较低，表明维生素D可以调控肠道MMP-7的表达，从而影响DEFA1的成熟。同时，体外细胞实验表明：1，25-二羟基维生素D3能够上调肠道细胞MMP-7的转录水平和蛋白水平。初步表明，维生素D通过调控MMP-7的表达影响DEFA1的成熟，而维生素D缺失，MMP-7下调从而DEFA1下调，进一步可能造成肠道菌群失调，导致多种慢性疾病的发生。

1,25(OH)₂VD₃ up regulates activation of α-defensins through induction of MMP-7 in mouse intestine

CHEN Zishuo, LIU Yu

College of Life Sciences, Sichuan University, Chengdu 610064, China

Abstract: The aim of this study was to find the role of VD in regulating the active form of α-defensin 1(DEFA1), one of the antibacterial peptides in mouse intestine. It showed that the active DEFA1 was much lower in VDR knock-out mice compared to the wild type(WT) mice. Both mRNA and protein of matrix metalloproteinase-7(MMP-7), the cleaved enzyme of DEFA1, as detected by immumohistochemical staining and qRT-PCR, were at a relatively low level. In vitro experiment showed that VD can induce the expression of MMP-7 in colon cells. Thus, it suggested that VD can regulate the expression of MMP-7. When VD was deficient, MMP-7 was down-regulated and so was the active form of DEFA1, it might lead to impairment of intestinal innate immunity and dysbiosis and drive chronic disorders.

Keywords: 1,25(OH)₂VD₃;Vitamin D receptor knock-out mice;matrix metalloproteinase-7;α-defensin

2016, 42(8): 57-63  收稿日期: 2016-3-20;收到修改稿日期: 2016-4-25

基金项目: 

作者简介: 陈子硕(1990-),女,江苏徐州市人,硕士研究生,专业方向为代谢综合征、肠道菌群细胞生物学。

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