山东医药2018，Vol.58Issue(9)：21-24,4.DOI:10.3969/j.issn.1002-266X.2018.09.006
LSD1在急性肾损伤肾纤维化中的保护作用及机制
Effects of LSD1 on renal fibrosis after acute kidney injury
摘要
Abstract
Objective To investigate the effects of histone lysine-specific demethylase1 (LSD1) on the development and progression of renal fibrosis after acute kidney injury (AKI).Methods Thirty SD rats were randomly divided into the control group,AKI 1-day group,AKI 1-week (AKI 1W) group,AKI 2-week (AKI 2W) group,AKI 4-week (AKI 4W) group,and AKI 8-week (AKI 8W)group;in the control group,the left kidney was resected and the right kidney was not treated;in the AKI groups,the left kidney was resected and we clamped the right renal pedicle for 40 min,then collected the heart blood and kidney tissues of rats at 1 d,1 w,2 w,4 w and 8 w,respectively.The human renal tubular epithelial cells (HK-2) were divided into the control group,AKI group,AKI + empty plasmid group,and AKI + LSD1 over-expression group.In the control group,we normally cultured the HK-2 cells;in the AKI group,HK-2 cells were cultured for 12 h under hypoxia and then normally cultured for 1 h;in the AKI + empty plasmid group,after the HK-2 cells were transfected with blank plasmid,they were first cultured for 12 h under hypoxia and then normally cultured for 1 h;in the AKI + LSD1 over-expression group,after the HK-2 cells were transfected with LSD1 plasmid,they were first cultured for 12 h under hypoxia and then normally cultured for 1 h.The expression levels of LSD1,H3K4me1,H3K4me2,TGF-β1,and fibrosis markers were detected by Western blotting in the renal tissues and HK-2 cells.We observed the LSD1 expression changes in the occurrence and development of renal fibrosis after AKI,as well as histone methylation and its impact on fibrosis.The specific mechanism of LSD1 on renal fibrosis was explored by chromosome immunoprecipitation (ChIP) technique.Results In the animal experiments,compared with the control group,the fibrosis indexes of AKI 1W,2W,4W and 8W groups were significantly higher,and the expression of TGF-β1,LSD1,and H3K4 methylation markers H3K4me1 and H3K4me2 increased (all P ＜0.05);there was no significant differences between AKI 1 d group and control group (P ＞ 0.05).In the cell experiments,compared with the AKI group and AKI + enpty plasmid group,the fibrosis indexes decreased significantly,and the expression of TGF-β1,H3K4 methylation markers H3K4me1 and H3K4me2 decreased in the AKI + LSD1 over-expression group (all P ＜ 0.05).In the cell experiment,compared with the control group,the expression of H3K4mel and H3K4me2 increased on TGF-β1 promoters in the AKI group and AKI + plasmid group (all P ＜0.05);compared with the AKI group and AKI + plasmid group,the expression of H3K4me1 and H3K4me2 on TGF-β1 promoters in the AKI + LSD1 over-expression group significantly decreased (P ＜ 0.05).Conclusion LSD1 plays a protective role in renal fibrosis after AKI by inducing demethylation of H3K4mel and H3K4me2 to decrease the expression of TGF-β.关键词
急性肾损伤/纤维化/组蛋白赖氨酸特异性去甲基化酶1/表观遗传修饰/组蛋白类/甲基化Key words
acute kidney injury/fibrosis/histone lysine specific demethylase 1/epigenetic modification/histones/methylation分类
医药卫生引用本文复制引用
赵晴,刘晓宇,刘航,杨海燕,徐岩..LSD1在急性肾损伤肾纤维化中的保护作用及机制[J].山东医药,2018,58(9):21-24,4.基金项目
国家自然科学基金面上项目(81170688 （）
81470973). （）
