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0018 Rev-rebα-mir122 Axis Activation Mediates Sleep Deprivation-induced Hepatic Inflammation By Enhancing Hmgb1 Expression

Sleep (New York, N.Y.), 2019-04, Vol.42 (Supplement_1), p.A7-A7 [Peer Reviewed Journal]

Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com. ;ISSN: 0161-8105 ;EISSN: 1550-9109 ;DOI: 10.1093/sleep/zsz067.017

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  • Title:
    0018 Rev-rebα-mir122 Axis Activation Mediates Sleep Deprivation-induced Hepatic Inflammation By Enhancing Hmgb1 Expression
  • Author: Xing, Chen ; Gu, Ye ; Huang, Xin ; Hu, Meiru ; Song, Lun
  • Subjects: Binding sites ; Inflammation ; Liver ; Sleep deprivation
  • Is Part Of: Sleep (New York, N.Y.), 2019-04, Vol.42 (Supplement_1), p.A7-A7
  • Description: Introduction Health consequences of sleep loss or insufficient sleep have been proved to be associated with increased inflammation, which is considered as a risk factor for various diseases, including cardiovascular, metabolic, neurodegenerative diseases and cancer. However, the inflammation occurred in targeted or injured tissues after sleep loss has not been fully revealed. High-mobility group box 1 (HMGB1) plays a critical role in triggering and sustaining inflammatory responses by inducing cytokine releasing and recruiting leucocytes. The aim of this study is to address whether sleep deprivation (SD) could induce hepatic HMGB1 upregulation and the underlying mechanism involved. Methods Samples of rat liver, blood and urine were collected after 48 h of SD. The expression levels of HMGB1, REV-ERBα and miR-122 were determined by ELISA, PCR and western blot assays. Binding sites of miR-122 within HMGB1-3’UTR were identified by luciferase reporter assay. Results SD induced increasing of HMGB1 expression in the rat liver, serum and urine. Interestingly, liver HMGB1 upregulation was only observed at the protein levels, while HMGB1 mRNA levels remained stable under the same conditions. Then, two miR-122 binding sites were identified within the 3’-UTR region of HMGB1. And the liver miR-122 expression levels were significantly decreased after SD. Furthermore, HMGB1 protein expression levels dramatically decreased in miR-122 mimic-transfected cells and significantly increased in miR-122 inhibitors-transfected cells compared with those in the control cells. Besides, SD inhibited the expression of central clock gene, REV-ERBα, in the liver. Knockdown of REV-ERBα expression significantly decreased miR-122 expression and increased HMGB1 expression. Conclusion Down regulation of liver REV-ERBα and miR-122 is involved in local HMGB1 upregulation induced by SD. In addition, HMGB1 might function as potential biomarker for indicating the hepatic inflammatory responses induced by SD. Support (If Any) Military Sciences Foundation of China (No. AWS17J014, BWS17J025), National Natural Sciences Foundation of China (81700759).
  • Publisher: Westchester: Oxford University Press
  • Language: English
  • Identifier: ISSN: 0161-8105
    EISSN: 1550-9109
    DOI: 10.1093/sleep/zsz067.017
  • Source: ProQuest One Psychology
    Alma/SFX Local Collection
    ProQuest Central
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