title: MicroRNA-133a regulates insulin-like growth factor-1 receptor expression and vascular smooth muscle cell proliferation in murine atherosclerosis.
abstract: OBJECTIVE
  MicroRNA-133a (miR-133a) and insulin-like growth factor-1 (IGF-1) are two different molecules known to regulate cardiovascular cell proliferation. This study tested whether miR-133a affects expression of IGF-1 receptor (IGF-1R) and proliferation of IGF-1-stimulated vascular smooth muscle cells (VSMC) in a murine model of atherosclerosis.
  
  
  RESULTS
  Expression of IGF-1R was analyzed by immuno-fluorescence and immuno-blotting, and miR-133a by qRT-PCR in the aortas of wild-type C57BL/6J (WT) and apolipoprotein-E deficient (ApoE(-/-)) mice. Compared to those in WT aortas, the IGF-1R and miR-133a levels were lower in ApoE(-/-) aortas. ApoE(-/-) VSMC grew slower than WT cells in the cultures with IGF-1-containing medium. MiR-133a-specific inhibitor decreased miR-133a, IGF-1R expression, IGF-1-stimulated VSMC growth in lipoprotein deficient media. By contrast, miR-133a precursor increased IGF-1R levels and promoted IGF-1-induced VSMC proliferation. In the luciferase-IGF-1R 3'UTR reporter system, the reporter luciferase activity was not inhibited in VSMC with miR-133a overexpression. IGF-1R mRNA half-life in ApoE(-/-) VSMC was shorter than that in WT VSMC. MiR-133a inhibitor reduced but precursor increased the mRNA half-life, although the effects appeared less striking in ApoE(-/-) VSMC than in WT cells.
  
  
  CONCLUSIONS
  MiR-133a serves as a stimulatory factor for IGF-1R expression through prolonging IGF-1R mRNA half-life. In atherosclerosis induced by ApoE deficiency, reduced miR-133a expression is associated with lower IGF-1R levels and suppressive VSMC growth. Administration of miR-133a precursor may potentiate IGF-1-stimulated VSMC survival and growth.
authors.affiliation: The Texas Heart Institute at St. Luke's Hospital, Houston, TX, USA; The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.affiliation: The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wassler
authors.affiliation: The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Lulu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Texas Heart Institute at St. Luke's Hospital, Houston, TX, USA.
authors.forename: Yangxin
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Texas Heart Institute at St. Luke's Hospital, Houston, TX, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Texas Heart Institute at St. Luke's Hospital, Houston, TX, USA; The Affiliated Hospital of Hainan Medical University, Haikou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Harnath
authors.initials: H
authors.lastname: Shelat
authors.affiliation: The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Williams
authors.affiliation: The Texas Heart Institute at St. Luke's Hospital, Houston, TX, USA; The University of Texas Medical School at Houston, Houston, TX, USA. Electronic address: yong-jian.geng@uth.tmc.edu.
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Geng
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D050197:Atherosclerosis / Q000097:blood* / Q000503:physiopathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C517731:Mirn1 microRNA, mouse; C517732:Mirn133 microRNA, mouse; D012333:RNA, Messenger; D017526:Receptor, IGF Type 1
keywords: Artery; Atherosclerosis; Insulin-like growth factor; MicroRNA; Smooth muscle cell