title: miRNA-1283 Regulates the PERK/ATF4 Pathway in Vascular Injury by Targeting ATF4.
abstract: BACKGROUND
  In our previous study, we found significant differences in the mRNA and microRNA (miRNA) levels among hypertensive patients with different degrees of vascular endothelial cells damage. These differences were closely associated with endoplasmic reticulum stress (ERS)-related proteins. Moreover, compared to the control group, the expression of transcription factor activating factor 4 (ATF4) was also found to be significantly different in the hypertensive patients with different degrees of vascular endothelial cells damage groups. These results were confirmed using gene prediction software, which showed synergistic effects between ATF4 and miR-1283. ATF4 is a key molecule in ERS. Three ERS pathways exist:protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and inositol-requiring enzyme-1 (IRE-1)-induced apoptosis. The PERK pathway is the most important and also includes the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and ATF4. In this report, we studied the regulatory effects of miR-1283 and ATF4 on the PERK-eIF2α-ATF4 signaling pathway using human umbilical vein endothelial cells (HUVECs) and mice.
  
  
  RESULTS
  We verified the relationship between miR-1283 and ATF4 using a luciferase activity assay and observed the regulatory effects of miR-1283 and ATF4 on the PERK-eIF2α-ATF4 signaling pathway in vivo and in vitro.
  
  
  CONCLUSIONS
  ATF4 is a target gene of miR-1283, which regulates the PERK-eIF2α-ATF4 signaling pathway by inhibiting ATF4, and it plays a critical role in inducing injury in HUVECs and mouse heart tissue.
authors.affiliation: Department of Chinese Medicine, Medical College of Jinan University, Guangzhou, 510632, Guangdong Province, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Chinese Medicine, Medical College of Jinan University, Guangzhou, 510632, Guangdong Province, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Chinese Medicine, Medical College of Jinan University, Guangzhou, 510632, Guangdong Province, PR China.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Chinese Medicine, Medical College of Jinan University, Guangzhou, 510632, Guangdong Province, PR China.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Chinese Medicine, Medical College of Jinan University, Guangzhou, 510632, Guangdong Province, PR China.
authors.forename: Liguo
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Laboratory Animals, Jinan University, Guangzhou, 510632, Guangdong Province, PR China.
authors.forename: Meixia
authors.identifier: http://orcid.org/0000-0001-5882-5783
authors.initials: M
authors.lastname: Fang
mesh_terms: D051701:Activating Transcription Factor 4 / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D004721:Endoplasmic Reticulum / Q000502:physiology; D004722:Endoribonucleases / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology; D006801:Humans; D020287:In Situ Nick-End Labeling; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D019892:eIF-2 Kinase / Q000502:physiology*
chemical_list: C497109:ATF4 protein, human; C581550:MIRN1283 microRNA, human; D035683:MicroRNAs; D051701:Activating Transcription Factor 4; D008156:Luciferases; C460640:EIF2AK3 protein, human; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D004722:Endoribonucleases