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MALAT1/miR‐185‐5p mediated high glucose‐induced oxidative stress, mitochondrial injury and cardiomyocyte apoptosis via the RhoA/ROCK pathway
To explore the underlying mechanism of lncRNA MALAT1 in the pathogenesis of diabetic cardiomyopathy (DCM). DCM models were confirmed in db/db mice. MiRNAs in myocardium were detected by miRNA sequencing. The interactions of miR‐185‐5p with MALAT1 and RhoA were validated by dual‐luciferase reporter a...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468660/ https://www.ncbi.nlm.nih.gov/pubmed/37395157 http://dx.doi.org/10.1111/jcmm.17835 |
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author | Wang, Ting Li, Na Yuan, Lingling Zhao, Mengnan Li, Guizhi Chen, Yanxia Zhou, Hong |
author_facet | Wang, Ting Li, Na Yuan, Lingling Zhao, Mengnan Li, Guizhi Chen, Yanxia Zhou, Hong |
author_sort | Wang, Ting |
collection | PubMed |
description | To explore the underlying mechanism of lncRNA MALAT1 in the pathogenesis of diabetic cardiomyopathy (DCM). DCM models were confirmed in db/db mice. MiRNAs in myocardium were detected by miRNA sequencing. The interactions of miR‐185‐5p with MALAT1 and RhoA were validated by dual‐luciferase reporter assays. Primary neonatal cardiomyocytes were cultured with 5.5 or 30 mmol/L D‐glucose (HG) in the presence or absence of MALAT1‐shRNA and fasudil, a ROCK inhibitor. MALAT1 and miR‐185‐5p expression were determined by real‐time quantitative PCR. The apoptotic cardiomyocytes were evaluated using flow cytometry and TUNEL staining. SOD activity and MDA contents were measured. The ROCK activity, phosphorylation of Drp1(S616), mitofusin 2 and apoptosis‐related proteins were analysed by Western blotting. Mitochondrial membrane potential was examined by JC‐1. MALAT1 was significantly up‐regulated while miR‐185‐5p was down‐regulated in myocardium of db/db mice and HG‐induced cardiomyocytes. MALAT1 regulated RhoA/ROCK pathway via sponging miR‐185‐5p in cardiomyocytes in HG. Knockdown of MALAT1 and fasudil all inhibited HG‐induced oxidative stress, and alleviated imbalance of mitochondrial dynamics and mitochondrial dysfunction, accompanied by reduced cardiomyocyte apoptosis. MALAT1 activated the RhoA/ROCK pathway via sponging miR‐185‐5p and mediated HG‐induced oxidative stress, mitochondrial damage and apoptosis of cardiomyocytes in mice. |
format | Online Article Text |
id | pubmed-10468660 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104686602023-09-01 MALAT1/miR‐185‐5p mediated high glucose‐induced oxidative stress, mitochondrial injury and cardiomyocyte apoptosis via the RhoA/ROCK pathway Wang, Ting Li, Na Yuan, Lingling Zhao, Mengnan Li, Guizhi Chen, Yanxia Zhou, Hong J Cell Mol Med Original Articles To explore the underlying mechanism of lncRNA MALAT1 in the pathogenesis of diabetic cardiomyopathy (DCM). DCM models were confirmed in db/db mice. MiRNAs in myocardium were detected by miRNA sequencing. The interactions of miR‐185‐5p with MALAT1 and RhoA were validated by dual‐luciferase reporter assays. Primary neonatal cardiomyocytes were cultured with 5.5 or 30 mmol/L D‐glucose (HG) in the presence or absence of MALAT1‐shRNA and fasudil, a ROCK inhibitor. MALAT1 and miR‐185‐5p expression were determined by real‐time quantitative PCR. The apoptotic cardiomyocytes were evaluated using flow cytometry and TUNEL staining. SOD activity and MDA contents were measured. The ROCK activity, phosphorylation of Drp1(S616), mitofusin 2 and apoptosis‐related proteins were analysed by Western blotting. Mitochondrial membrane potential was examined by JC‐1. MALAT1 was significantly up‐regulated while miR‐185‐5p was down‐regulated in myocardium of db/db mice and HG‐induced cardiomyocytes. MALAT1 regulated RhoA/ROCK pathway via sponging miR‐185‐5p in cardiomyocytes in HG. Knockdown of MALAT1 and fasudil all inhibited HG‐induced oxidative stress, and alleviated imbalance of mitochondrial dynamics and mitochondrial dysfunction, accompanied by reduced cardiomyocyte apoptosis. MALAT1 activated the RhoA/ROCK pathway via sponging miR‐185‐5p and mediated HG‐induced oxidative stress, mitochondrial damage and apoptosis of cardiomyocytes in mice. John Wiley and Sons Inc. 2023-07-03 /pmc/articles/PMC10468660/ /pubmed/37395157 http://dx.doi.org/10.1111/jcmm.17835 Text en © 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Wang, Ting Li, Na Yuan, Lingling Zhao, Mengnan Li, Guizhi Chen, Yanxia Zhou, Hong MALAT1/miR‐185‐5p mediated high glucose‐induced oxidative stress, mitochondrial injury and cardiomyocyte apoptosis via the RhoA/ROCK pathway |
title |
MALAT1/miR‐185‐5p mediated high glucose‐induced oxidative stress, mitochondrial injury and cardiomyocyte apoptosis via the RhoA/ROCK pathway |
title_full |
MALAT1/miR‐185‐5p mediated high glucose‐induced oxidative stress, mitochondrial injury and cardiomyocyte apoptosis via the RhoA/ROCK pathway |
title_fullStr |
MALAT1/miR‐185‐5p mediated high glucose‐induced oxidative stress, mitochondrial injury and cardiomyocyte apoptosis via the RhoA/ROCK pathway |
title_full_unstemmed |
MALAT1/miR‐185‐5p mediated high glucose‐induced oxidative stress, mitochondrial injury and cardiomyocyte apoptosis via the RhoA/ROCK pathway |
title_short |
MALAT1/miR‐185‐5p mediated high glucose‐induced oxidative stress, mitochondrial injury and cardiomyocyte apoptosis via the RhoA/ROCK pathway |
title_sort | malat1/mir‐185‐5p mediated high glucose‐induced oxidative stress, mitochondrial injury and cardiomyocyte apoptosis via the rhoa/rock pathway |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468660/ https://www.ncbi.nlm.nih.gov/pubmed/37395157 http://dx.doi.org/10.1111/jcmm.17835 |
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