MiR-197 Participates in Lipopolysaccharide-Induced Cardiomyocyte Injury by Modulating SIRT1.

Miaomiao Liu,Xiantong Cao,Tao Shi,Yang Yan,Ying Zhang,Francesco Paciullo

doi:10.1155/2022/7687154

Abstract

Sepsis is a systemic inflammation and is capable of inducing myocarditis, which is a major leading cause of death in patients. Studies have found that miR-197 is correlated with the prognosis of patients with inflammatory heart disease, but its effect on sepsis-induced cardiomyocyte injury remains unclear. We treated H9c2 cells with lipopolysaccharide (LPS), then detected the cell viability via the cell counting kit-8 (CCK-8) assay and quantified miR-197 expression via quantitative real-time polymerase chain reaction (qRT-PCR). Then, we investigated the role of miR-197 in LPS-induced H9c2 cells by CCK-8 assay, flow cytometry, lactate dehydrogenase (LDH) measurement, enzyme-linked immunosorbent assay (ELISA), qRT-PCR, and western blot. Subsequently, silent information regulator 1 (SIRT1) was downregulated in H9c2 cells to explore its interaction with miR-197 under LPS induction. LPS induced miR-197 overexpression in H9c2 cells. LPS restrained viability, the expressions of B-cell lymphoma-2 (Bcl-2) and SIRT1, but promoted apoptosis, LDH release, and levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), acetyl (AC)-p53, BCL2-associated X (Bax), and cleaved caspase-3 in H9c2 cells. miR-197 inhibition reversed the effects of LPS on H9c2 cells. The protective role of miR-197 downregulation in LPS-induced H9c2 cells was reversed by SIRT1 silencing. miR-197 contributed to LPS-induced cardiomyocyte injury by modulating SIRT1, which might be used as a molecular marker in the management of sepsis.

Highlights

Sepsis is a systemic inflammatory response due to microbial infection, manifested by a range of symptoms such as shortness of breath, tachycardia, fever, and abnormal white blood cell counts, which can lead to septic shock and multiorgan failure in severe cases [1,2,3]
LPS Suppressed Viability and Induced miR-197 Overexpression in H9c2 Cells. e cell counting kit 8 (CCK-8) assay demonstrated that the viability was inhibited in H9c2 cells treated with LPS as compared with that in control cells (p < 0.001) (Figure 1(a)). rough qRT-PCR, we noticed that miR-197 level was upregulated in LPS-induced H9c2 cells compared with that in control cells (p < 0.001) (Figure 1(b))
Cell functional experiments revealed that LPS significantly inhibited viability but promoted apoptosis of H9c2 cells as compared with the control group, and these LPS-induced effects were partially reversed by the miR-197 inhibitor (p < 0.01) (Figures 1(d)–1(f ))

Summary

Introduction

Sepsis is a systemic inflammatory response due to microbial infection, manifested by a range of symptoms such as shortness of breath, tachycardia, fever, and abnormal white blood cell counts, which can lead to septic shock and multiorgan failure in severe cases [1,2,3]. Despite progress in understanding of the pathology of sepsis, the molecular mechanism of the myocardial inflammation response for septic still needs to be refined [8]. Some progress has been made in the study of miR-197 in cardiovascular diseases, and in particular, its abnormal expression has been shown to be involved in the occurrence and development of myocardial infarction, coronary artery disease, heart failure, and so on [13,14,15]. There are few studies focusing on the mechanism or biological function of miR-197 in sepsis-induced myocarditis

Methods

Results

Conclusion