首页|KLF4通过促进自噬减轻高糖浓度下巨噬细胞胆固醇沉积

KLF4通过促进自噬减轻高糖浓度下巨噬细胞胆固醇沉积

Krüppel-like factor 4 alleviated cholesterol deposition in macrophages by promoting autophagy at high glucose concentration

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目的 观察Krüppel样因子4(KLF4)对高糖处理的巨噬细胞胆固醇沉积的影响,并探讨其作用机制是否与巨噬细胞自噬相关.方法 10只Balb/c小鼠随机分为正常对照(NC)组和糖尿病(DM)组,每组5只.建立DM小鼠模型,给予高脂饮食后检测小鼠主动脉KLF4蛋白表达水平.人白血病单核细胞THP-1诱导为巨噬细胞后分为LV-NC组、LV-KLF4组、si-NC组、si-KLF4组.观察过表达或敲低KLF4表达后,THP-1巨噬细胞胆固醇含量、细胞凋亡、自噬相关蛋白及蛋白激酶B/雷帕霉素靶蛋白(AKT/mTOR)信号通路相关蛋白的表达变化.结果 DM组小鼠主动脉KLF4蛋白表达水平低于NC组(P<0.05).KLF4过表达可显著降低高糖条件下的THP-1巨噬细胞胆固醇积累,增加苄氯素1(Beclin1)表达,降低P62表达,提高微管相关蛋白1轻链3(LC3)荧光强度,减少细胞凋亡(P<0.05),抑制AKT/mTOR信号通路相关蛋白表达(P<0.05).敲低KLF4表达后,结果反之.结论 KLF4通过促进自噬减轻高糖浓度下巨噬细胞胆固醇沉积.
Objective To observe the effect of Krüppel-like factor 4(KLF4)on cholesterol deposition in macrophages treated with high glucose,and to explore the mechanism related to macrophage autophagy.Methods Ten Balb/c mice were randomly divided into the normal control(NC,n=5)group and the DM group(n=5).A diabetic mouse model was established,and the expression level of KLF4 protein in aorta was detected after high fat diet.After induction of THP-1 monocytes into macrophages,they were divided into the LV-NC group,the LV-KLF4 group,the si-NC group and the si-KLF4 group.Changes of cholesterol content,cell apoptosis and the expression level of autophagy related proteins and AKT/mTOR signaling pathway related proteins in THP-1 macrophages were observed after overexpression or knockout of KLF4.Results The expression level of KLF4 protein in aorta of diabetic mice was lower in the DM group than that of the NC group(P<0.05).Meanwhile,under high glucose concentration,overexpression of KLF4 in THP-1 macrophages significantly decreased cholesterol deposition,cell apoptosis and P62 expression,increased Beclin1 expression,LC3 fluorescence intensity and also inhibited AKT/mTOR signaling pathway related protein expression(P<0.05).After knocking down KLF4 expression,the results were reversed.Conclusion KLF4 alleviates cholesterol deposition in THP-1 macrophages by promoting autophagy under high glucose concentration.

autophagymacrophagesKrüppel-like factor 4high glucosecholesterol deposition

张睿、陈思思、王彤丹、于珮

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天津医科大学朱宪彝纪念医院血液净化中心、天津市内分泌研究所、国家卫健委激素与发育重点实验室、天津市代谢性疾病重点实验室(邮编 300134)

自噬 巨噬细胞 Krüppel样因子4 高糖 胆固醇沉积

天津市教委科研计划项目

2019KJ193

2024

天津医药
天津市医学科学技术信息研究所

天津医药

CSTPCD
影响因子:1.107
ISSN:0253-9896
年,卷(期):2024.52(10)