Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov;77(4):577-587.
doi: 10.1007/s13105-021-00822-z. Epub 2021 Jun 19.

miR-124-3p targeted SIRT1 to regulate cell apoptosis, inflammatory response, and oxidative stress in acute myocardial infarction in rats via modulation of the FGF21/CREB/PGC1α pathway

Yun-Jie Wei  1 , Jun-Feng Wang  1 , Fei Cheng  1 , Hai-Jun Xu  1 , Jia-Juan Chen  1 , Jian Xiong  1 , Jing Wang  2
Affiliations

miR-124-3p targeted SIRT1 to regulate cell apoptosis, inflammatory response, and oxidative stress in acute myocardial infarction in rats via modulation of the FGF21/CREB/PGC1α pathway

Yun-Jie Wei et al. J Physiol Biochem. 2021 Nov.

Abstract

To investigate whether miR-124-3p influences cell apoptosis, inflammatory response, and oxidative stress in rats with acute myocardial infarction (AMI) by mediating the SIRT1/FGF21/CREB/PGC1α pathway. A dual-luciferase reporter gene assay was performed to verify the relationship between miR-124-3p and SIRT1. AMI rats were established via coronary artery ligation after injection with agomiR-124-3p, antagomiR-124-3p, and/or SIRT1 siRNA, and triphenyltetrazolium chloride (TTC), HE, and TUNEL stainings were performed. Bio-Plex rat cytokine assays were performed to determine proinflammatory factor levels. qRT-PCR and Western blotting were used to examine the mRNA and protein expression, respectively. The activity levels of antioxidant enzymes in myocardial tissues were also measured. miR-124-3p was confirmed to target SIRT1 in the H9C2 cells. AMI rats exhibited increased miR-124-3p expression and decreased SIRT1 expression in myocardial tissues. HE staining showed a disorganized cell arrangement and inflammatory cell infiltration in the myocardial tissues of the AMI rats, which was more severe in the rats injected with SIRT1 and agomiR-124-3p but was ameliorated in those treated with antagomiR-124-3p. Moreover, the AMI rats in the antagomiR-124-3p group presented with a reduction in infarct area with an increase in antioxidant enzyme activity, Bcl-2 expression, and activation of the FGF21/CREB/PGC1α pathway, as well as a decrease in cell apoptosis rate, Bax and Caspase-3 expression, and levels of proinflammatory factors, effects that were reversed by si-SIRT1. Inhibiting miR-124-3p expression may activate the FGF21/CREB/PGC1α pathway to reduce cell apoptosis, alleviate the inflammatory response, and attenuate oxidative stress in AMI rats by targeting SIRT1. Graphical abstract.

Keywords: AMI; FGF21/CREB/PGC1α; SIRT1; miR-124-3p.

PubMed Disclaimer

References

    1. Aoi W (2014) Frontier impact of microRNAs in skeletal muscle research: a future perspective. Front Physiol 5:495 - PubMed
    1. Bao Q, Chen L, Li J, Zhao M, Wu S, Wu W, Liu X (2017) Role of microRNA-124 in cardiomyocyte hypertrophy inducedby angiotensin II. Cell Mol Biol (Noisy-le-grand) 63(4):23–27
    1. Brennan GP, Dey D, Chen Y, Patterson KP, Magnetta EJ, Hall AM, Dube CM, Mei YT, Baram TZ (2016) Dual and opposing roles of microRNA-124 in epilepsy are mediated through inflammatory and NRSF-dependent gene networks. Cell Rep 14(10):2402–2412 - PubMed - PMC
    1. Chen P, Pan J, Zhang X, Shi Z, Yang X (2018) The role of microRNA-181a in myocardial fibrosis following myocardial infarction in a rat model. Med Sci Monit 24:4121–4127 - PubMed - PMC
    1. Fu B, Zhang J, Zhang X, Zhang C, Li Y, Zhang Y, He T, Li P, Zhu X, Zhao Y, Zhang Y, Wang X (2014) Alpha-lipoic acid upregulates SIRT1-dependent PGC-1alpha expression and protects mouse brain against focal ischemia. Neuroscience. 281:251–257 - PubMed

Substances

LinkOut - more resources