miR-1290对非酒精性脂肪性肝病的调控机制研究OACSTPCD
Regulatory mechanism of miR-1290 in non-alcoholic fatty liver disease
目的 探讨miRNAs是否参与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的发病过程以及miR-1290对NAFLD GH/IGF1轴调控的可能机制.方法 通过GenBank GEO数据库,Targetscan、mirBase、miRanda等miRNA生物数据库以及大量文献阅读筛选出在NAFLD中异常表达的miRNAs,再通过GO和KEGG分析靶基因预测软件筛选出与GH/IGF1轴基因相关的miRNAs;利用1 nmol/L游离脂肪酸(free fatty acid,FFA)诱导人肝细胞HL-7702(L02)并建立NAFLD的细胞模型(L02 NAFLD);通过不同浓度的rhGH、rhIGF1干预L02细胞及NAFLD细胞;观察不同浓度干预后相关miRNAs的基因表达变化;使用细胞转染技术进行验证.结果 与L02 细胞相比,L02 NAFLD 细胞中 miR-16、miR-1290、miR-122 的表达上调(P<0.05).25、250 ng/mL rhGH 及 50、500 ng/mL rhIGF1分别干预L02细胞和L02 NAFLD细胞,干预后两组细胞的TG水平均较干预前明显上调(P<0.05);miR-1290 和 miR-16 表达受抑制,尤其是 miR-1290 表达明显下调(P<0.05).mimics miR-1290,L02 NAFLD 组中 GHR、IGFBP3、FASN 的表达差异均有统计学意义(P=0.021、0.045、0.020,均<0.05),PPAR-γ、SREBP-1c水平差异无统计学意义(P>0.05).结论 miRNAs在NAFLD中表达异常,miR-1290在NAFLD中表达上调,miR-1290可能通过GH/IGF1参与NAFLD脂质代谢及胰岛素抵抗发病过程.
Objective To explore the role and potential regulatory mechanism of miR-1290 in non-alcoholic fatty liver disease(NAFLD).Methods GenBank GEO database,Targetscan,mirBase,miRanda biological databases were screened to find out miRNAs abnormally expressions in NAFLD,and GO and KEGG analysis target gene prediction databases were used to select miRNAs related to GH-IGF1 axis.NAFLD was induced in HL-7702(L02)cells to establish L02 NAFLD cell line.L02 cells(control group)and NAFLD cells were treated with 25,250 ng/mL rhGH and 50,500 ng/mL rhIGF1,respectively;and the expression of miRNAs was detected with RT-qPCR and verified by cell transfection.Results In NAFLD group,the expressions of miR-1290,miR-16,miR-122 were significantly higher than those in control(P<0.05);after treatment of rhGH and rhIGF1 the expression levels in NAFLD group were decreased,compared to those in control group(P<0.05).In L02 NAFLD cells transfected with mimics miR-1290,the expression levels of GHR,IGFBP3,FASN mRNA were significantly higher than those in control group(P<0.05).Conclusion MiRNAs are abnormally expressed in NAFLD,miR-1290 has higher expression in NAFLD cells,which may act on lipid metabolism and insulin resistance in NAFLD through GH/IGF1 axis.
邹琳;孙菲;李映璇;陈霞;马俊花
上海市浦东新区公利医院内分泌科,上海 200135
临床医学
非酒精性脂肪性肝病miRNAs胰岛素抵抗脂代谢GH/IGF1轴
non-alcoholic fatty liver diseasemiRNAsinsulin resistancelipid metabolismGH/IGF1 axis
《同济大学学报(医学版)》 2024 (004)
488-495 / 8
上海市浦东新区卫生系统优秀青年医学人才培养计划(PWRq2020-30);上海市卫生健康委员会项目(202040315);上海市浦东新区公利医院青年英才基金(GLRq2018-02)
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