Research Paper Volume 15, Issue 9 pp 3826—3838
miR-926-3p influences myocardial injury in septic mice through regulation of mTOR signaling pathway by targeting TSC1
- 1 Department of Cardiology, The Second Hospital of Shanxi Medical University, Shanxi 030001, People’s Republic of China
Received: February 18, 2022 Accepted: April 24, 2023 Published: May 11, 2023
https://doi.org/10.18632/aging.204716How to Cite
Copyright: © 2023 Yan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: The purpose of this study is to investigate the influence of miR-926-3p on myocardial injury and its mechanisms.
Methods: An animal model of sepsis was constructed by CLP, and animals were randomly divided into 4 groups: C group, miR-926-3p inhibitor group, CLP + NC group, and CLP + miR-926-3p inhibitor group.
Results: Compared with those in C group, echocardiographic parameters remarkably declined in CLP + NC group. Compared with CLP + NC group, miR-926-3p inhibitor group indicated elevated echocardiographic parameters in mice, pathological improvement tendency of myocardial tissues and distinct reduction in cardiomyocyte apoptosis. It could be observed by electron microscopy that the number of lysosomes in miR-926-3p inhibitor group was greatly increased relative to CLP + NC group. Immunofluorescence exhibited that the number of green fluorescent puncta was significantly higher in miR-926-3p inhibitor group as compared to that in CLP + NC group. The autophagic flow was verified by observing the relative expression of LC3II at different times. The results of Western blotting manifested that miR-926-3p inhibitor up-regulated mTOR-related protein expressions and down-regulated the protein expression of p-mTOR. LPS was adopted to induce cardiomyocyte injury in vitro, and the results confirmed that, identical to in vivo experiments, miR-926-3p inhibitor was able to up-regulate the protein expressions of mTOR-related protein and down-regulate p-mTOR protein expression in cardiomyocytes. After addition of MHY1485, The expression of mTOR-related proteins changes in each group.
Conclusion: Inhibition of miR-926-3p enhances autophagy through regulation of the mTOR signaling pathway, thus ameliorating myocardial injury in septic mice.
Abbreviations
miR: micro ribonucleic acid; CLP: cecum ligation and puncture; C: control; NC: negative control; TSC1: tuberous sclerosis complex 1; ATG: autophagy-related protein; LC3II: light chain 3 II; p-mTOR: phosphorylated mammalian target of rapamycin; LPS: Lipopolysaccharide.