title: MicroRNA hsa-let-7g targets lectin-like oxidized low-density lipoprotein receptor-1 expression and inhibits apoptosis in human smooth muscle cells.
abstract: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been identified as a major receptor for oxidatively modified low density lipoprotein (ox-LDL) in endothelial cells and smooth muscle cells (SMCs). MicroRNAs are small non-coding RNAs that regulate gene expression. Very few studies have reported regulation of LOX-1 expression by microRNAs in SMCs. The present study demonstrates that the microRNA hsa-let-7g can inhibit LOX-1 expression in a time- and dose-dependent fashion, and subsequently inhibit ox-LDL uptake in and proliferation of human aortic SMCs. We also show that hsa-let-7g can reduce SMC apoptosis by down-regulation of cytochrome c and Smac/Diablo and upregulation of Bcl-xL and Bcl-2 expression. Furthermore, we show that hsa-let-7g reduces ox-LDL-induced increase in the expression of NADPH oxidase (p22(phox) and p47(phox) subunits) and subsequent intracellular reactive oxygen species generation, phosphorylation of p44/42 mitogen-activated protein kinase and nuclear factor-kappaB p65 expression. These observations suggest that hsa-let-7g is a critical regulator of SMC apoptosis, and may be suitable for therapeutic intervention in disease states characterized by LOX-1 over-expression.
authors.affiliation: Department of Medicine, Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences, Little Rock, Arkansas 72212, USA.
authors.forename: Zufeng
authors.initials: Z
authors.lastname: Ding
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.forename: Magomed
authors.initials: M
authors.lastname: Khaidakov
authors.forename: Shijie
authors.initials: S
authors.lastname: Liu
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D045304:Cytochromes c / Q000096:biosynthesis; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008077:Lipoproteins, LDL / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D019255:NADPH Oxidases / Q000096:biosynthesis; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000096:biosynthesis; D014157:Transcription Factors / Q000378:metabolism; D051020:bcl-X Protein / Q000096:biosynthesis
chemical_list: D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D035683:MicroRNAs; D024101:Mitochondrial Proteins; C495137:OLR1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; D051996:Transcription Factor RelA; D014157:Transcription Factors; C478359:WDR77 protein, human; D051020:bcl-X Protein; C487931:mirnlet7 microRNA, human; C099252:oxidized low density lipoprotein; D045304:Cytochromes c; D019255:NADPH Oxidases