Dataset Information

Down-regulated HDAC1 and up-regulated microRNA-124-5p recover myocardial damage of septic mice.

ABSTRACT: Studies have revealed the relationship between histone deacetylases (HDACs)/microRNAs (miRNAs) and sepsis, but little has ever investigated the mechanism of HDAC1/miR-124-5p in sepsis. Herein, we studied the impacts of HDAC1/miR-124-5p on myocardial damage of septic mice via regulating high-mobility group box chromosomal protein 1 (HMGB1). Septic mice were induced by cecal ligation and puncture. HDAC1, miR-124-5p and HMGB1 expression in myocardial tissues of septic mice were detected. Septic mice were injected with HDAC1 low expression-, miR-124-5p high expression- or HMGB1 low expression-related structures to observe cardiac function, inflammatory response, oxidative stress response, myocardial pathological changes and apoptosis in myocardial tissues of septic mice. The relationship of HDAC1/miR-124-5p/HMGB1 was verified. HDAC1 and HMGB1 expression were upregulated while miR-124-5p expression was decreased in myocardial tissues of septic mice. Restored miR-124-5p/depleted HDAC1 or HMGB1 recovered the cardiac function, improved cardiac function, inflammatory response, oxidative stress response, myocardial pathological changes and inhibit ed cardiomyocyte apoptosis in septic mice. HDAC1 bound to miR-124-5p which directly targeted HMGB1. This study suggests that down-regulated HDAC1 or up-regulated miR-124-5p recovers myocardial damage of septic mice via decreasing HMGB1.

SUBMITTER: Nong R

PROVIDER: S-EPMC9278975 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Down-regulated HDAC1 and up-regulated microRNA-124-5p recover myocardial damage of septic mice.

Nong Rongmao R Qin Chunyan C Lin Qiqing Q Lu Yi Y Li Jun J

Bioengineered 20220301 3

Studies have revealed the relationship between histone deacetylases (HDACs)/microRNAs (miRNAs) and sepsis, but little has ever investigated the mechanism of HDAC1/miR-124-5p in sepsis. Herein, we studied the impacts of HDAC1/miR-124-5p on myocardial damage of septic mice via regulating high-mobility group box chromosomal protein 1 (HMGB1). Septic mice were induced by cecal ligation and puncture. HDAC1, miR-124-5p and HMGB1 expression in myocardial tissues of septic mice were detected. Septic mic ...[more]

PMID: 35285407

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Project description:Altered levels and functions of microRNAs (miRs) have been associated with inflammatory bowel diseases (IBDs), although little is known about their roles in pediatric IBD. We investigated whether colonic mucosal miRs are altered in children with ulcerative colitis (UC).We used a library of 316 miRs to identify those that regulate phosphorylation of signal transducer and activator of transcription 3 (STAT3) in NCM460 human colonocytes incubated with interleukin-6. Levels of miR-124 were measured by real-time polymerase chain reaction analysis of colon biopsies from pediatric and adult patients with UC and patients without IBD (controls), and of HCT-116 colonocytes incubated with 5-aza-2'-deoxycytidine (5-AZA). Methylation of the MIR124 promoter was measured by quantitative methylation-specific polymerase chain reaction.Levels of phosphorylated STAT3 and the genes it regulates (encoding vascular endothelial growth factor (VEGF), BCL2, BCLXL, and matrix metallopeptidase 9 [MMP9]) were increased in pediatric patients with UC compared with control tissues. Overexpression of miR-124, let-7, miR-125, miR-26, or miR-101 reduced STAT3 phosphorylation by ? 75% in NCM460 cells; miR-124 had the greatest effect. miR-124 was down-regulated specifically in colon tissues from pediatric patients with UC and directly targeted STAT3 messenger RNA (mRNA). Levels of miR-124 were decreased, whereas levels of STAT3 phosphorylation increased in colon tissues from pediatric patients with active UC compared with those with inactive disease. In addition, levels of miR-124 and STAT3 were inversely correlated in mice with experimental colitis. Down-regulation of miR-124 in tissues from children with UC was attributed to hypermethylation of its promoter region. Incubation of HCT-116 colonocytes with 5-AZA up-regulated miR-124 and reduced levels of STAT3 mRNA.miR-124 appears to regulate the expression of STAT3. Reduced levels of miR-124 in colon tissues of children with active UC appear to increase expression and activity of STAT3, which could promote inflammation and the pathogenesis of UC in children.

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Dataset Information

Down-regulated HDAC1 and up-regulated microRNA-124-5p recover myocardial damage of septic mice.

Publications

Down-regulated HDAC1 and up-regulated microRNA-124-5p recover myocardial damage of septic mice.

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