Abstract
Sepsis-induced cardiac dysfunction can lead to death in sepsis. In this case, we targeted to explore in detail the relative mechanism of microRNA (miR)-124-3p in sepsis-induced myocardial injury via the specific protein 1/histone deacetylase 4/hypoxia-inducing factor 1α (SP1/HDAC4/HIF-1α) axis. Septic rats were modeled by cecal ligation puncture while in vitro septic cardiomyocyte H9C2 were induced by lipopolysaccharide (LPS). miR-124-3p/SP1/HDAC4/HIF-1α expression levels in myocardial tissues of septic rats and LPS-treated H9C2 cells were measured. miR-124-3p overexpression and SP1 silencing assays were implemented on LPS-treated H9C2 cells to explore theirs actions in inflammation, oxidative stress and cell apoptosis. The interactions of miR-124-3p, SP1, and HDAC4 were testified. miR-124-3p was lowly expressed while SP1, HDAC4, and HIF-1α were highly expressed in sepsis. Upregulation of miR-124-3p ameliorated inflammation, oxidative stress, and apoptosis of LPS-treated H9C2 cells. Silencing SP1 improved LPS-induced damage to cardiomyocytes. miR-124-3p targeted SP1 and HDAC4 interacted with SP1. SP1 overexpression antagonized miR-124-3p upregulation-induced improvements in LPS-induced cardiomyocyte damage. This study illustrates that miR-124-3p improves myocardial injury in septic rats through targeted regulation of SP1 to mediate HDAC4/HIF-1α.
Highlights
Sepsis is featured by inflammatory disorders, which is an inflammatory immune response stimulated by infection [1]
In the experiments, decreased Left ventricular systolic pressure (LVSP) value and increased left ventricular end diastolic pressure (LVEDP) value were seen in septic rats (Fig. 1B, C), suggesting the impaired myocardial contraction and diastolic function
MiR-124-3p expression was tested in cardiomyocytes after silencing Specific protein 1 (SP1), and the results presented that silencing SP1 did not affect the expression of miR124-3p (Fig. 4O)
Summary
Sepsis is featured by inflammatory disorders, which is an inflammatory immune response stimulated by infection [1]. Patients with sepsis complain a variety of immunological changes that lead to immunosuppression [2]. Sepsisrelated mortality reduction depends on early diagnosis and prompt empirical antibiotic therapy [3]. About 40–60% of septic patients manifest myocardial dysfunction that is characterized by myocardial systolic and diastolic dysfunction [4]. Several methods have been developed to prevent sepsis-induced myocardial dysfunction, but effective treatments are still inaccessible. Facing to the challenge to treat myocardial injury induced by sepsis, much more studies shall be conducted to explore novel treatment options
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