title: Pioglitazone up-regulates long non-coding RNA MEG3 to protect endothelial progenitor cells via increasing HDAC7 expression in metabolic syndrome.
abstract: Long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) is expressed in endothelial cells and involved in angiogenesis and vascular function. It was proposed that MEG3 participates in the process of endothelial progenitor cells (EPCs) functions in metabolic syndrome (MetS). In this study, the circulating EPCs number and function were decreased in MetS subjects. The MEG3 expression was expressed at a lower level and microRNA-140-5p (miR-140-5p) was expressed at a higher level in circulating EPCs of subjects with MetS. Pioglitazone reversed the alterations of EPCs function and the expression levels of MEG3 and miR-140-5p in EPCs. In bone marrow-derived EPCs exposed to palmitate, down-regulation of miR-140-5p canceled the increase of MEG3 expression level induced by Pioglitazone. Overexpression of MEG3 resulted in the down-regulation of miR-140-5p. The luciferase reporter assay and RIP assay showed that MEG3 targeted miR-140-5p. In addition, the HDAC7 expression levels were regulated by miR-140-5p and MEG3. These findings demonstrated that Pioglitazone up-regulated MEG3 expression to protect EPCs via decreasing miR-140-5p expression and increasing HDAC7 expression in MetS, which may be a novel therapeutic target for preventing and treating MetS.
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, China. Electronic address: hhzzliu@163.com.
authors.forename: H Z
authors.initials: HZ
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Q Y
authors.initials: QY
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: D T
authors.initials: DT
authors.lastname: Qi
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: M W
authors.initials: MW
authors.lastname: Li
authors.affiliation: Department of Echocardiography, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: W Q
authors.initials: WQ
authors.lastname: Guo
authors.affiliation: Department of Endocrinology and Metabolism, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Y H
authors.initials: YH
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: L Y
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: C Y
authors.initials: CY
authors.lastname: Gao
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology; D002452:Cell Count; D019610:Cytoprotection / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D000077205:Pioglitazone; D062085:RNA, Long Noncoding / Q000235:genetics*; D045162:Thiazolidinediones / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D008055:Lipids; C498907:MEG3 non-coding RNA, human; D035683:MicroRNAs; C544302:Mirn140 microRNA, human; D062085:RNA, Long Noncoding; D045162:Thiazolidinediones; C543273:HDAC7 protein, human; D006655:Histone Deacetylases; D000077205:Pioglitazone
keywords: Endothelial progenitor cells; HDAC7; Metabolic syndrome; lncRNA; miR-140