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

doi:10.11958/20240283

Abstract

Abstract:

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.

Key words: autophagy, macrophages, Krüppel-like factor 4, high glucose, cholesterol deposition

CLC Number:

R587.1

Figures/Tables 9

References 24

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基因	引物序列（5'→3'）
KLF4-siRNA	上游：GGAGAAGACACUGCGUCAATT
	下游：UUGACGCAGUGUCUUCUCCTT
KLF4-siRNA NC	上游：UUCUCCGAACGUGUCACGUTT
	下游：ACGUGACACGUUCGGAGAATT

基因	引物序列（5'→3'）
KLF4-siRNA	上游：GGAGAAGACACUGCGUCAATT
	下游：UUGACGCAGUGUCUUCUCCTT
KLF4-siRNA NC	上游：UUCUCCGAACGUGUCACGUTT
	下游：ACGUGACACGUUCGGAGAATT

组别	n	血糖/（mmol/L）	TG/（mmol/L）	TC/（mmol/L）
NC组	5	5.40±0.35	1.26±0.11	2.25±0.10
DM组	5	17.17±1.47	2.25±0.07	7.13±0.84
t		15.600^＊＊	15.030^＊＊	11.550^＊＊

组别	n	血糖/（mmol/L）	TG/（mmol/L）	TC/（mmol/L）
NC组	5	5.40±0.35	1.26±0.11	2.25±0.10
DM组	5	17.17±1.47	2.25±0.07	7.13±0.84
t		15.600^＊＊	15.030^＊＊	11.550^＊＊

组别	Beclin1/ β-actin	LC3/ β-actin	P62/ β-actin	p-AKT/ AKT	p-mTOR/ mTOR
LV-NC组	1.00±0.20	0.99±0.16	1.01±0.07	1.01±0.17	1.00±0.17
LV-KLF4组	1.40±0.28	1.42±0.23	0.83±0.10	0.68±0.22	0.76±0.15
t	7.822^＊	9.811^＊	5.678^＊	8.837^＊	19.970^＊＊
si-NC组	1.00±0.16	0.96±0.13	1.13±0.09	0.95±0.23	1.07±0.12
si-KLF4组	0.78±0.10	0.54±0.08	1.47±0.17	1.15±0.17	1.40±0.10
t	5.949^＊	13.500^＊＊	7.921^＊	5.415^＊	25.840^＊＊