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Dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncRNA TUG1/miR-194/SIRT1 signaling pathway
BACKGROUND: Liver injury seriously threatens the health of people. Meanwhile, dexmedetomidine hydrochloride (DEX) can protect against liver injury. However, the mechanism by which Dex mediates the progression of liver injury remains unclear. Thus, this study aimed to investigate the function of DEX...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157629/ https://www.ncbi.nlm.nih.gov/pubmed/34039367 http://dx.doi.org/10.1186/s12950-021-00287-3 |
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author | Gu, Xiao-Xia Xu, Xiao-Xia Liao, Hui-Hua Wu, Ruo-Na Huang, Wei-Ming Cheng, Li-Xia Lu, Yi-Wen Mo, Jian |
author_facet | Gu, Xiao-Xia Xu, Xiao-Xia Liao, Hui-Hua Wu, Ruo-Na Huang, Wei-Ming Cheng, Li-Xia Lu, Yi-Wen Mo, Jian |
author_sort | Gu, Xiao-Xia |
collection | PubMed |
description | BACKGROUND: Liver injury seriously threatens the health of people. Meanwhile, dexmedetomidine hydrochloride (DEX) can protect against liver injury. However, the mechanism by which Dex mediates the progression of liver injury remains unclear. Thus, this study aimed to investigate the function of DEX in oxygen and glucose deprivation (OGD)-treated hepatocytes and its underlying mechanism. METHODS: In order to investigate the function of DEX in liver injury, WRL-68 cells were treated with OGD. Cell viability was measured by MTT assay. Cell apoptosis was detected by flow cytometry. Inflammatory cytokines levels were measured by ELISA assay. The interaction between miR-194 and TUG1 or SIRT1 was detected by dual-luciferase reporter. Gene and protein levels were measured by qPCR or western blotting. RESULTS: DEX notably reversed OGD-induced inflammation and apoptosis in WRL-68 cell. Meanwhile, the effect of OGD on TUG1, SIRT1 and miR-194 expression in WRL-68 cells was reversed by DEX treatment. However, TUG1 knockdown or miR-194 overexpression reversed the function of DEX in OGD-treated WRL-68 cells. Moreover, TUG1 could promote the expression of SIRT1 by sponging miR-194. Furthermore, knockdown of TUG1 promoted OGD-induced cell growth inhibition and inflammatory responses, while miR-194 inhibitor or SIRT1 overexpression partially reversed this phenomenon. CONCLUSIONS: DEX could suppress OGD-induced hepatocyte apoptosis and inflammation by mediation of TUG1/miR-194/SIRT1 axis. Therefore, this study might provide a scientific basis for the application of DEX on liver injury treatment. |
format | Online Article Text |
id | pubmed-8157629 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-81576292021-05-28 Dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncRNA TUG1/miR-194/SIRT1 signaling pathway Gu, Xiao-Xia Xu, Xiao-Xia Liao, Hui-Hua Wu, Ruo-Na Huang, Wei-Ming Cheng, Li-Xia Lu, Yi-Wen Mo, Jian J Inflamm (Lond) Research BACKGROUND: Liver injury seriously threatens the health of people. Meanwhile, dexmedetomidine hydrochloride (DEX) can protect against liver injury. However, the mechanism by which Dex mediates the progression of liver injury remains unclear. Thus, this study aimed to investigate the function of DEX in oxygen and glucose deprivation (OGD)-treated hepatocytes and its underlying mechanism. METHODS: In order to investigate the function of DEX in liver injury, WRL-68 cells were treated with OGD. Cell viability was measured by MTT assay. Cell apoptosis was detected by flow cytometry. Inflammatory cytokines levels were measured by ELISA assay. The interaction between miR-194 and TUG1 or SIRT1 was detected by dual-luciferase reporter. Gene and protein levels were measured by qPCR or western blotting. RESULTS: DEX notably reversed OGD-induced inflammation and apoptosis in WRL-68 cell. Meanwhile, the effect of OGD on TUG1, SIRT1 and miR-194 expression in WRL-68 cells was reversed by DEX treatment. However, TUG1 knockdown or miR-194 overexpression reversed the function of DEX in OGD-treated WRL-68 cells. Moreover, TUG1 could promote the expression of SIRT1 by sponging miR-194. Furthermore, knockdown of TUG1 promoted OGD-induced cell growth inhibition and inflammatory responses, while miR-194 inhibitor or SIRT1 overexpression partially reversed this phenomenon. CONCLUSIONS: DEX could suppress OGD-induced hepatocyte apoptosis and inflammation by mediation of TUG1/miR-194/SIRT1 axis. Therefore, this study might provide a scientific basis for the application of DEX on liver injury treatment. BioMed Central 2021-05-26 /pmc/articles/PMC8157629/ /pubmed/34039367 http://dx.doi.org/10.1186/s12950-021-00287-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Gu, Xiao-Xia Xu, Xiao-Xia Liao, Hui-Hua Wu, Ruo-Na Huang, Wei-Ming Cheng, Li-Xia Lu, Yi-Wen Mo, Jian Dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncRNA TUG1/miR-194/SIRT1 signaling pathway |
title | Dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncRNA TUG1/miR-194/SIRT1 signaling pathway |
title_full | Dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncRNA TUG1/miR-194/SIRT1 signaling pathway |
title_fullStr | Dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncRNA TUG1/miR-194/SIRT1 signaling pathway |
title_full_unstemmed | Dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncRNA TUG1/miR-194/SIRT1 signaling pathway |
title_short | Dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncRNA TUG1/miR-194/SIRT1 signaling pathway |
title_sort | dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncrna tug1/mir-194/sirt1 signaling pathway |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157629/ https://www.ncbi.nlm.nih.gov/pubmed/34039367 http://dx.doi.org/10.1186/s12950-021-00287-3 |
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