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MiR-21 participates in LPS-induced myocardial injury by targeting Bcl-2 and CDK6.
- Source :
-
Inflammation research : official journal of the European Histamine Research Society ... [et al.] [Inflamm Res] 2022 Feb; Vol. 71 (2), pp. 205-214. Date of Electronic Publication: 2022 Jan 22. - Publication Year :
- 2022
-
Abstract
- Objective: This study aimed to investigate the relationship between miR-21 and lipopolysaccharide (LPS)-induced myocardial injury and its molecular and regulatory mechanisms.<br />Methods: We constructed LPS-mediated myocardial injury model using C57BL/6J mice and H9c2 cells. In-vivo, in-vitro, RIP and dual-luciferase reporter assays were used to determine the effect of miR-21 on myocardial injury.<br />Results: In-vivo and in-vitro results showed that the expression of miR-21 was increased in LPS-treated H9c2 cells and myocardial tissues of mice, and the pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) and NF-κB pathway were activated in LPS-treated H9c2 cells. Besides, the B-cell lymphoma-2 (Bcl-2) and cyclin-dependent kinase 6 (CDK6) expression levels decreased, while Bax and cleaved caspase 9 levels increased in LPS-treated H9c2 cells. Inhibition of miR-21 could suppress LPS-induced apoptosis, inflammatory reactions and NF-κB activation to attenuate LPS-induced myocardial injury in H9c2 cells, and effectively improve survival of mice with sepsis. Most importantly, Bcl-2 and CDK6 were found to be the direct target of miR-21 using dual-luciferase reporter and RNA immunoprecipitation assays. Further gain-of-function assay demonstrated that Bcl-2 or CDK6 over-expression promoted the protective effects of miR-21 inhibitor on LPS-mediated myocardial cells.<br />Conclusion: Our findings revealed that the down-regulation or antagonism of miR-21 protects myocardial cells against LPS-induced apoptosis and inflammation through up-regulating Bcl-2 and CDK6 expression, which provided a new insight for prevention and treatment of myocardial injury.<br /> (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
- Subjects :
- Animals
Apoptosis drug effects
Cells, Cultured
Heart physiology
Inflammation prevention & control
Lipopolysaccharides toxicity
Male
Mice
Mice, Inbred C57BL
MicroRNAs antagonists & inhibitors
Myocytes, Cardiac drug effects
Myocytes, Cardiac pathology
NF-kappa B physiology
Cyclin-Dependent Kinase 6 genetics
Heart drug effects
MicroRNAs physiology
Proto-Oncogene Proteins c-bcl-2 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1420-908X
- Volume :
- 71
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Inflammation research : official journal of the European Histamine Research Society ... [et al.]
- Publication Type :
- Academic Journal
- Accession number :
- 35064305
- Full Text :
- https://doi.org/10.1007/s00011-021-01535-1