Downregulation of MALAT1 alleviates saturated fatty acid-induced myocardial inflammatory injury via the miR-26a/HMGB1/TLR4/NF-κB axis

Downregulation of MALAT1 alleviates saturated fatty acid-induced myocardial inflammatory injury via the miR-26a/HMGB1/TLR4/NF-κB axis

Pengyu Jia,1 Nan Wu,2 Dalin Jia,1 Yingxian Sun11Department of Cardiology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People‘s Republic of China; 2The Central Laboratory of the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, Peo...

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Autores principales: Jia P, Wu N, Jia D, Sun Y
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2019
Materias:
metastasis-associated lung adenocarcinoma transcript 1
saturated fatty acids
microRNA
high mobility group box-1 protein
inflammation
Specialties of internal medicine
RC581-951
Acceso en línea:https://doaj.org/article/a03cf65736f04d468545fc85a693965d
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spelling oai:doaj.org-article:a03cf65736f04d468545fc85a693965d2021-12-02T03:33:37ZDownregulation of MALAT1 alleviates saturated fatty acid-induced myocardial inflammatory injury via the miR-26a/HMGB1/TLR4/NF-κB axis1178-7007https://doaj.org/article/a03cf65736f04d468545fc85a693965d2019-05-01T00:00:00Zhttps://www.dovepress.com/downregulation-of-malat1-alleviates-saturated-fatty-acid-induced-myoca-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Pengyu Jia,1 Nan Wu,2 Dalin Jia,1 Yingxian Sun11Department of Cardiology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People‘s Republic of China; 2The Central Laboratory of the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People‘s Republic of ChinaPurpose: The increased level of saturated fatty acids (SFAs) is found in patients with diabetes, obesity, and other metabolic disorders. SFAs can induce lipotoxic damage to cardiomyocytes, but the mechanism is unclear. The long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) acts as a key regulator in palmitic acid (PA)-induced hepatic steatosis, but its role in PA-induced myocardial lipotoxic injury is still unknown. The aim of this study was to explore the role and underlying mechanism of MALAT1 in PA-induced myocardial lipotoxic injury.Methods: MALAT1 expression in PA-treated human cardiomyocytes (AC16 cells) was detected by RT-qPCR. The effect of MALAT1 on PA-induced myocardial injury was measured by Cell Counting Kit-8, lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) assays. Apoptosis was detected by flow cytometry. The activities of cytokines and nuclear factor (NF)-κB were detected by enzyme-linked immunosorbent assay. The interaction between MALAT1 and miR-26a was evaluated by a luciferase reporter assay and RT-qPCR. The regulatory effects of MALAT1 on high mobility group box 1 (HMGB1) expression were evaluated by RT-qPCR and western blotting.Results: MALAT1 was significantly upregulated in cardiomyocytes after PA treatment. Knockdown of MALAT1 increased the viability of PA-treated cardiomyocytes, decreased apoptosis, and reduced the levels of LDH, CK-MB, TNF-α, and IL-1β. Moreover, we found that MALAT1 specifically binds to miR-26a and observed a reciprocal negative regulatory relationship between these factors. We further found that the downregulation of MALAT1 represses HMGB1 expression, thereby inhibiting the activation of the Toll-like receptor 4 (TLR4)/NF-κB-mediated inflammatory response. These repressive effects were rescued by an miR-26a inhibitor.Conclusion: We demonstrate that MALAT1 is induced by SFAs and its downregulation alleviates SFA-induced myocardial inflammatory injury via the miR-26a/HMGB1/TLR4/NF-κB axis. Our findings provide new insight into the mechanism underlying myocardial lipotoxic injury.Keywords: metastasis-associated lung adenocarcinoma transcript 1, saturated fatty acids, microRNA, high mobility group box-1 protein, inflammationJia PWu NJia DSun YDove Medical Pressarticlemetastasis-associated lung adenocarcinoma transcript 1saturated fatty acidsmicroRNAhigh mobility group box-1 proteininflammationSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 12, Pp 655-665 (2019)
institution DOAJ
collection DOAJ
language EN
topic metastasis-associated lung adenocarcinoma transcript 1
saturated fatty acids
microRNA
high mobility group box-1 protein
inflammation
Specialties of internal medicine
RC581-951
spellingShingle metastasis-associated lung adenocarcinoma transcript 1
saturated fatty acids
microRNA
high mobility group box-1 protein
inflammation
Specialties of internal medicine
RC581-951
Jia P
Wu N
Jia D
Sun Y
Downregulation of MALAT1 alleviates saturated fatty acid-induced myocardial inflammatory injury via the miR-26a/HMGB1/TLR4/NF-κB axis
description Pengyu Jia,1 Nan Wu,2 Dalin Jia,1 Yingxian Sun11Department of Cardiology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People‘s Republic of China; 2The Central Laboratory of the First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People‘s Republic of ChinaPurpose: The increased level of saturated fatty acids (SFAs) is found in patients with diabetes, obesity, and other metabolic disorders. SFAs can induce lipotoxic damage to cardiomyocytes, but the mechanism is unclear. The long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) acts as a key regulator in palmitic acid (PA)-induced hepatic steatosis, but its role in PA-induced myocardial lipotoxic injury is still unknown. The aim of this study was to explore the role and underlying mechanism of MALAT1 in PA-induced myocardial lipotoxic injury.Methods: MALAT1 expression in PA-treated human cardiomyocytes (AC16 cells) was detected by RT-qPCR. The effect of MALAT1 on PA-induced myocardial injury was measured by Cell Counting Kit-8, lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) assays. Apoptosis was detected by flow cytometry. The activities of cytokines and nuclear factor (NF)-κB were detected by enzyme-linked immunosorbent assay. The interaction between MALAT1 and miR-26a was evaluated by a luciferase reporter assay and RT-qPCR. The regulatory effects of MALAT1 on high mobility group box 1 (HMGB1) expression were evaluated by RT-qPCR and western blotting.Results: MALAT1 was significantly upregulated in cardiomyocytes after PA treatment. Knockdown of MALAT1 increased the viability of PA-treated cardiomyocytes, decreased apoptosis, and reduced the levels of LDH, CK-MB, TNF-α, and IL-1β. Moreover, we found that MALAT1 specifically binds to miR-26a and observed a reciprocal negative regulatory relationship between these factors. We further found that the downregulation of MALAT1 represses HMGB1 expression, thereby inhibiting the activation of the Toll-like receptor 4 (TLR4)/NF-κB-mediated inflammatory response. These repressive effects were rescued by an miR-26a inhibitor.Conclusion: We demonstrate that MALAT1 is induced by SFAs and its downregulation alleviates SFA-induced myocardial inflammatory injury via the miR-26a/HMGB1/TLR4/NF-κB axis. Our findings provide new insight into the mechanism underlying myocardial lipotoxic injury.Keywords: metastasis-associated lung adenocarcinoma transcript 1, saturated fatty acids, microRNA, high mobility group box-1 protein, inflammation
format article
author Jia P
Wu N
Jia D
Sun Y
author_facet Jia P
Wu N
Jia D
Sun Y
author_sort Jia P
title Downregulation of MALAT1 alleviates saturated fatty acid-induced myocardial inflammatory injury via the miR-26a/HMGB1/TLR4/NF-κB axis
title_short Downregulation of MALAT1 alleviates saturated fatty acid-induced myocardial inflammatory injury via the miR-26a/HMGB1/TLR4/NF-κB axis
title_full Downregulation of MALAT1 alleviates saturated fatty acid-induced myocardial inflammatory injury via the miR-26a/HMGB1/TLR4/NF-κB axis
title_fullStr Downregulation of MALAT1 alleviates saturated fatty acid-induced myocardial inflammatory injury via the miR-26a/HMGB1/TLR4/NF-κB axis
title_full_unstemmed Downregulation of MALAT1 alleviates saturated fatty acid-induced myocardial inflammatory injury via the miR-26a/HMGB1/TLR4/NF-κB axis
title_sort downregulation of malat1 alleviates saturated fatty acid-induced myocardial inflammatory injury via the mir-26a/hmgb1/tlr4/nf-κb axis
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/a03cf65736f04d468545fc85a693965d
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