Back to Search
Start Over
Downregulation of growth arrest‑specific transcript 5 alleviates palmitic acid‑induced myocardial inflammatory injury through the miR‑26a/HMGB1/NF‑κB axis
- Source :
- Molecular Medicine Reports.
- Publication Year :
- 2018
- Publisher :
- Spandidos Publications, 2018.
-
Abstract
- Palmitic acid (PA) can induce lipotoxic damage to cardiomyocytes, although its precise mechanism of action has not been completely elucidated. Growth arrest‑specific transcript 5 (GAS5) is a long noncoding RNA that serves a regulatory role in several pathological processes, including tumorigenesis, stroke, cardiac fibrosis and osteoarthritis; however, its role in PA‑induced myocardial injury remains elusive. The present study aimed to explore the role and underlying mechanism of GAS5 on PA‑induced myocardial injury. The expression of GAS5 in PA‑treated cardiomyocytes (H9c2 cells) was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and its effects on PA‑induced myocardial injury were measured by Cell Counting Kit‑8 and lactate dehydrogenase (LDH) assays. The activities of cytokines and nuclear factor (NF)‑κB were also detected by enzyme‑linked immunosorbent assay, while interactions between GAS5 and microRNA (miR)‑26a were evaluated by luciferase reporter assay and RT‑qPCR. The regulation of GAS5 on high mobility group box 1 (HMGB1) expression was detected by RT‑qPCR and western blotting. The results demonstrated that GAS5 was significantly upregulated in cardiomyocytes following treatment with PA. GAS5‑knockdown increased the viability of PA‑treated cardiomyocytes and reduced the activity of LDH, tumor necrosis factor‑α and interleukin‑1β. Furthermore, the present study identified that GAS5 specifically binds to miR‑26a, and a reciprocal negative regulation exists between the two. The present study also demonstrated that GAS5 downregulation inhibited HMGB1 expression and NF‑κB activation, while these suppressive effects were mediated by miR‑26a. In conclusion, the present study demonstrated that PA can induce GAS5 expression and that the downregulation of GAS5 alleviated PA‑induced myocardial inflammatory injury through the miR‑26a/HMGB1/NF‑κB axis. These data may provide a novel insight into the mechanism of myocardial lipotoxic injury.
- Subjects :
- 0301 basic medicine
Cancer Research
Cardiac fibrosis
Palmitic Acid
HMGB1
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Downregulation and upregulation
Lactate dehydrogenase
microRNA
Genetics
medicine
Animals
RNA, Small Nucleolar
Myocytes, Cardiac
HMGB1 Protein
Molecular Biology
biology
NF-kappa B
NF-κB
medicine.disease
Rats
MicroRNAs
Myocarditis
030104 developmental biology
Gene Expression Regulation
Oncology
Mechanism of action
chemistry
Gene Knockdown Techniques
030220 oncology & carcinogenesis
biology.protein
Cancer research
Cytokines
Molecular Medicine
RNA Interference
Tumor necrosis factor alpha
medicine.symptom
Signal Transduction
Subjects
Details
- ISSN :
- 17913004 and 17912997
- Database :
- OpenAIRE
- Journal :
- Molecular Medicine Reports
- Accession number :
- edsair.doi.dedup.....d8af9576bac0e494dec16ccb04cb6fba