MicroRNA-155-5p/EPAS1/interleukin 6 pathway participated in the protection function of sphingosylphosphorylcholine to ischemic cardiomyocytes

Autor: Jing Zhao, Chen-chen Lu, Wenjing Sun, Jinrun Zhou, Yu-juan Yao, Wei-hua Kong
Rok vydání: 2020
Předmět:
0301 basic medicine
STAT3 Transcription Factor
Vascular Endothelial Growth Factor A
animal structures
Cardiotonic Agents
Transcription
Genetic
Phosphorylcholine
Regulator
Myocardial Ischemia
Down-Regulation
Apoptosis
030226 pharmacology & pharmacy
Models
Biological
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Western blot
Sphingosine
microRNA
medicine
Basic Helix-Loop-Helix Transcription Factors
Animals
Humans
Myocytes
Cardiac
RNA
Messenger
General Pharmacology
Toxicology and Pharmaceutics
Phosphorylation
Rats
Wistar
Interleukin 6
STAT3
Cell Nucleus
biology
medicine.diagnostic_test
Base Sequence
Chemistry
Interleukin-6
fungi
EPAS1
Biological activity
General Medicine
Cell Hypoxia
Cell biology
MicroRNAs
030104 developmental biology
HEK293 Cells
biology.protein
Fibroblast Growth Factor 2
Signal Transduction
Zdroj: Life sciences. 264
ISSN: 1879-0631
Popis: Aim Previous research in our laboratory found that a biologically active sphingomyelin metabolite, sphingosylphosphorylcholine (SPC), can inhibit myocardial cell apoptosis caused by ischemia with an unknown mechanism. Here, we aimed to study the possible participation of EPAS1 in the protection process of SPC. Methods The rat cardiomyocytes deprived of serum were used to mimic ischemic-caused apoptosis, then treated with or without SPC. The expression and nuclear shift of EPAS1 were detected by western blot and immunofluorescence, and its function was studied using its siRNA. Key finding Our research shows that SPC inhibited serum starvation caused cardiomyocyte apoptosis, accompanied by the up-regulation and nucleus translocation of EPAS1. EPAS1 levels did not change when its transcript was blocked by Actinomycin D, which prompted us to search for a post-transcription mechanism for its increased expression, and finally found that miR-155-5p, regulated by STAT3, was a new post-transcription regulator to EPAS1. Further investigation found that EPAS1 participated in the protective effect of SPC is mainly achieved by activating the downstream target gene, interleukin-6 (IL-6). Significance Our results expand our understanding of the biological functions of SPC, and bring a new pathway as a potential therapeutic target to the treatment of cardiovascular diseases caused by myocardial apoptosis.
Databáze: OpenAIRE
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