Characteristics of transcription factors KLF2 and KLF4 regulating gene expression related to vascular homeostasis in human endothelial cells
10.20039/j.cnki.1007-3949.2024.05.002
- VernacularTitle:转录因子KLF2和KLF4调控人血管内皮细胞血管稳态相关基因表达的特征
- Author:
Meiming SU
1
;
Wenqi ZHAO
;
Yaping ZHAO
;
Suowen XU
Author Information
1. 中国科学技术大学附属第一医院内分泌与代谢病研究所 代谢健康与泛血管病安徽省重点实验室,安徽省合肥市 230001
- Keywords:
Krüppel-like factor 2;
Krüppel-like factor 4;
vascular homeostasis;
endothelial cell
- From:
Chinese Journal of Arteriosclerosis
2024;32(5):375-385
- CountryChina
- Language:Chinese
-
Abstract:
Aim Krüppel-like factor(KLF)2 and 4 are two core transcription factors closely related to vascular homeostasis,with multiple protective effects such as anti-inflammatory,anti-calcification and anti-thrombotic.The aim of this study is to elucidate and validate the vascular homeostasis related gene profile co-regulated by KLF2 and KLF4 in endo-thelial cells.Methods Human umbilical vein endothelial cells(HUVEC)were treated with adenovirus(Ad-KLF2 or Ad-KLF4)and control virus(Ad-NC)for 24 h,RNA was extracted from the cells and analyzed by transcriptomic sequen-cing.The sequencing results of overexpressed KLF2 and KLF4 were superimposed with the sequencing results of reported KLF2/KLF4 double-gene knockout mice.The selected differential expression genes were verified by real-time fluorescence quantitative PCR in HUVEC treated with Ad-KLF2 or Ad-KLF4,and in HUVEC treated with atorvastatin or resveratrol.Results Transcriptomic superposition revealed 256 differential expression genes were up-regulated by KLF2 and KLF4,and KEGG analysis showed that differential expression genes were enriched in hypertrophic cardiomyopa-thy,arrhythmogenic right ventricular cardiomyopathy,dilated cardiomyopathy,ECM-receptor interaction and focal adhesion;there were 145 differential expression genes down-regulated by KLF2 and KLF4,and KEGG analysis showed that differential expression genes were enriched in microRNA of cancer,mineral absorption,glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate,p53 signaling pathway and biosynthesis of amino acids.Finally,six novel genes regulated by KLF2 and KLF4 were obtained.Conclusion FGFR3,SEMA4B,SEMA6A,PTX3,FABP4 and FABP5 may be novel genes that regulate vascular homeostasis in endothelial cells by the transcription factors KLF2 and KLF4.
