title: A novel role for the Krüppel-like factor 14 on macrophage inflammatory response and atherosclerosis development.
abstract: Genome-wide association studies have shown that Krüppel-like factor 14 (KLF14) is associated with both Type 2 diabetes mellitus and lipid metabolism. However, its role in chronic inflammatory responses and the pathogenesis of atherosclerosis remains unknown. The present study was designed to investigate both in vivo and in vitro the impact of KLF14 on chronic inflammatory responses and atherosclerosis. ApoE KO mice, a well-established animal model of atherosclerosis, had higher expressions of KLF14 in aorta tissues than that in C57BL/6 J mice when fed the high-fat diet (HFD) or standard chow diet. Adenovirus-mediated KLF14 knockdown markedly reduced the circulating levels of proinflammatory cytokines and the formation of atherosclerotic lesions in HFD-fed ApoE KO mice. In the in vitro study, KLF14 overexpression in the RAW264.7 macrophages significantly increased the expressions of inflammatory cytokines, total cholesterol (TC), cholesteryl ester (CE), and the ratio of CE to TC in the cells treated with acetylated low-density lipoproteins (AcLDL). Conversely, KLF14 knockdown remarkably attenuated AcLDL-induced increase in TC, CE, and the ratio of CE to TC as well as the expressions of inflammatory cytokines. Furthermore, up-regulation or down-regulation of KLF14 markedly elevated or inhibited the phosphorylation levels of p38 MAPK and ERK1/2 in AcLDL-stimulated RAW264.7 macrophages, respectively. Importantly, treatment with p38 MAPK or ERK1/2 inhibitor nullified the effects of KLF14 on inflammatory cytokine expressions in the cells. These data demonstrate an important role for KLF14 expression in atherosclerotic lesion formation.
authors.affiliation: Department of Endocrinology, Yongchuan Hospital, Chongqing Medical University, 402160, Chongqing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Endocrinology, Yongchuan Hospital, Chongqing Medical University, 402160, Chongqing, China.
authors.forename: Ruomei
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Yongchuan Hospital, Chongqing Medical University, 402160, Chongqing, China.
authors.forename: Chengpan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010, Chongqing, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Jian
authors.affiliation: Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, 400010, Chongqing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Yongchuan Hospital, Chongqing Medical University, 402160, Chongqing, China; Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010, Chongqing, China. Electronic address: gangyiyang@163.com.
authors.forename: Gangyi
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Yongchuan Hospital, Chongqing Medical University, 402160, Chongqing, China. Electronic address: zhiyong8568@163.com.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D015151:Immunoblotting; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000067996:RAW 264.7 Cells; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016207:Cytokines; C558181:Klf14 protein, mouse; D051741:Kruppel-Like Transcription Factors
keywords: Atherosclerosis; Inflammatory; Krüppel-like factor 14; Lipid metabolism