Back to Search
Start Over
Identification of Nrf2-responsive microRNA networks as putative mediators of myocardial reductive stress
- Source :
- Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021), Scientific Reports
- Publication Year :
- 2021
- Publisher :
- Nature Portfolio, 2021.
-
Abstract
- Although recent advances in the treatment of acute coronary heart disease have reduced mortality rates, few therapeutic strategies exist to mitigate the progressive loss of cardiac function that manifests as heart failure. Nuclear factor, erythroid 2 like 2 (Nfe2l2, Nrf2) is a transcriptional regulator that is known to confer transient myocardial cytoprotection following acute ischemic insult; however, its sustained activation paradoxically causes a reductive environment characterized by excessive antioxidant activity. We previously identified a subset of 16 microRNAs (miRNA) significantly diminished in Nrf2-ablated (Nrf2−/−) mouse hearts, leading to the hypothesis that increasing levels of Nrf2 activation augments miRNA induction and post-transcriptional dysregulation. Here, we report the identification of distinct miRNA signatures (i.e. “reductomiRs”) associated with Nrf2 overexpression in a cardiac-specific and constitutively active Nrf2 transgenic (caNrf2-Tg) mice expressing low (TgL) and high (TgH) levels. We also found several Nrf2 dose-responsive miRNAs harboring proximal antioxidant response elements (AREs), implicating these “reductomiRs” as putative meditators of Nrf2-dependent post-transcriptional regulation. Analysis of mRNA-sequencing identified a complex network of miRNAs and effector mRNAs encoding known pathological hallmarks of cardiac stress-response. Altogether, these data support Nrf2 as a putative regulator of cardiac miRNA expression and provide novel candidates for future mechanistic investigation to understand the relationship between myocardial reductive stress and cardiac pathophysiology.
- Subjects :
- 0301 basic medicine
NF-E2-Related Factor 2
Transgene
Science
Cardiology
Regulator
Mice, Transgenic
030204 cardiovascular system & hematology
Biology
environment and public health
Antioxidants
Article
Gene regulatory networks
Mice
03 medical and health sciences
0302 clinical medicine
microRNA
Transcriptional regulation
Animals
Humans
Antioxidant Response Elements
Heart Failure
Multidisciplinary
Base Sequence
Effector
Myocardium
Heart
respiratory system
Cytoprotection
Cardiovascular biology
NFE2L2
Cell biology
Mice, Inbred C57BL
MicroRNAs
Oxidative Stress
030104 developmental biology
Gene Expression Regulation
Medicine
Gene ontology
Biomarkers
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....cf2a800252cdf9a1b96daebc480b9d68