山西医科大学学报2026，Vol.57Issue(1)：23-32,10.DOI:10.13753/j.issn.1007-6611.2026.01.004
miR-92a通过抑制KLF2和KLF4表达促进心肌细胞肥大
MiR-92a promotes cardiomyocyte hypertrophy by suppressing KLF2 and KLF4 expression
摘要
Abstract
Objective To investigate the role of miR-92a in the process of cardiomyocyte hypertrophy and its correlation with the signaling pathways of its target genes,Krüppel-like factor 2(KLF2)and Krüppel-like factor 4(KLF4).Methods Twenty-four 8-week-old C57BL/6J mice were randomly divided into control group,model group and miR-92a inhibitor(LNA-92a)group,with 8 mice in each group.The mice in model group and LNA-92a group received continuous subcutaneous infusion of angiotensin Ⅱ(AngⅡ)at a dose of 1 µg/(kg·min)for 28 d from day 8 to establish cardiomyocyte hypertrophy models.The mice in LNA-92a group received intravenous injection of LNA-92a at a dose of 16 mg/kg via tail vein at day 1 and day 18,the mice in model group received equivalent injection of the miR-92a inhibitor control(LNA-Ctrl)at the same time points,while the mice in control group received an equivalent volume of normal saline.All mice were euthanized at day 36.AC16 cardiomyocytes were cultured in vitro and randomly divided into three groups:negative control group,AngⅡ model group and AngⅡ+miR-92a inhibitor(anti-miR-92a)intervention group.Real-time quantitative PCR(RT-qPCR)was used to detect the mRNA levels of miR-92a and its target genes(KLF2,KLF4),and miR-483 and its target genes(CTGF,TGF-β)in serum and myocardial tissue of mice and cardiomyocytes.Western blot was used to detect the protein expression levels of KLF2,KLF4,CTGF and TGF-β in myocardial tissue of mice and cardiomyocytes.Immunofluorescence staining was used to compare the expression levels of CTGF in cardiomyocytes.Results Compared with control group,the mice in model group exhibited increased expression of miR-92a and decreased expression of miR-483 in serum and myocardial tissue(P<0.01),decreased mRNA and protein levels of KLF2 and KLF4 in myocardial tissue(P<0.01),and increased mRNA and protein levels of CTGF and TGF-β in myocardial tissue(P<0.01).Compared with model group,the mice in LNA-92a group showed decreased expression of miR-92a and increased expression of miR-483 in serum and myocardial tissue(P<0.05),increased KLF2 protein levels and KLF4 mRNA and protein levels in myocardial tissue(P<0.01),a trend toward increased KLF2 mRNA in myocardial tissue(P=0.059),and decreased mRNA and protein levels of CTGF and TGF-β in myocardial tissue(P<0.05).Compared with negative control group,the AC16 cardiomyocytes in AngⅡ model group exhibited increased miR-92a expression(P<0.01),decreased KLF2 and KLF4 mRNA and protein levels(P<0.01),decreased miR-483 expression(P<0.05),and increased CTGF and TGF-β mRNA and protein levels(P<0.01).Compared with AngⅡ model group,the miR-92a expression in AC16 cardiomyocytes decreased in AngⅡ+anti-miR-92a intervention group(P<0.01),KLF2 and KLF4 mRNA and protein levels increased(P<0.01),miR-483 expression increased(P<0.05),and CTGF and TGF-β mRNA and protein levels decreased(P<0.01).Compared with negative control group,CTGF relative fluorescence intensity in AC16 cardiomyocytes significantly increased in AngⅡ model group(P<0.01);compared with AngⅡ model group,CTGF relative fluorescence intensity in AC16 cardiomyocytes significantly decreased in AngⅡ+anti-miR-92a intervention group(P<0.01).Conclusion miR-92a may induce cardiomyocyte hypertrophy by suppressing KLF2 and KLF4 expression,thereby downregulating miR-483 expression.The antagonism of miR-92a expression could alleviate the cardiomyocyte hypertrophy by increasing KLF2/KLF4 and miR-483 expressions.关键词
血管紧张素Ⅱ/心肌细胞肥大/miR-92a/KLF2/KLF4/miR-483/CTGF/TGF-βKey words
angiotensinⅡ/cardiomyocyte hypertrophy/miR-92a/KLF2/KLF4/miR-483/CTGF/TGF-β分类
医药卫生引用本文复制引用
夏宇航,李俊,王兰,庞娟,杨维,尚粉青..miR-92a通过抑制KLF2和KLF4表达促进心肌细胞肥大[J].山西医科大学学报,2026,57(1):23-32,10.基金项目
国家自然科学基金面上项目(82370406) （82370406）
陕西省三秦英才特支计划创新领军人才项目 （）
