KLF15 Transcriptionally Activates ATG14 to Promote Autophagy and Attenuate Damage of ox-LDL-Induced HAECs.

Abstract

Kruppel-like factor 15 (KLF15) is involved in many cardiovascular diseases and is abnormally expressed in atherosclerosis (AS), but the regulatory mechanism of KLF15 in AS has not been reported so far. RT-qPCR was used to detect the expression of KLF15 and ATG14 in AS patients. Subsequently, human aortic endothelial cells (HAECs) were induced by oxidized low densitylipoprotein (ox-LDL), and the expression of KLF15 in model cells was detected. KLF15 was overexpressed in cells by lipofection transfection, and then CCK8, flow cytometry, Western blot, ELISA, and related assay kits were used to detect cell viability, apoptosis, inflammatory response as well as oxidative stress, respectively. The targeted regulatory relationship between KLF15 and autophagy-related 14 (ATG14) was detected by ChIP and luciferase reporter assays. Following ATG14 silencing in KLF15-overexpressing cells, immunofluorescence and Western blot were used to detect the autophagy. Finally, after the addition of 3-Methyladenine (3-MA), an autophagy inhibitor, the aforementioned experiments were conducted again to further explore the mechanism. The expression of KLF15 and ATG14 were decreased in AS patients and ox-LDL-induced HAECs. Overexpression of KLF15 protected ox-LDL-induced HAECs from damage, which might be achieved through transcriptional regulation of ATG14. In addition, KLF15 could promote autophagy through transcriptional activation of ATG14. KLF15 transcriptionally activated ATG14 to promote autophagy and attenuate damage of ox-LDL-induced HAECs.