MiR-141 attenuates sepsis-induced cardiomyopathy by targeting DAPK1

Abstract

Objective To discuss the possible effects of microRNA-141 (miR-141) in sepsis-induced cardiomyopathy (SIC) via targeting death-associated protein kinase 1 (DAPK1). Methods An SIC mouse model was constructed by abdominal injection of lipopolysaccharide (LPS) and divided into control, LPS, LPS + pre-miR-141, and LPS + anti-miR-141 groups. Hemodynamic indicators and heart function indexes of mice were detected. ELISA was used to determine the serum levels of inflammatory cytokines, while TUNEL staining to observe the apoptosis of myocardial cells of mice, as well as qRT-PCR and Western blotting to clarify the expression of miR-141 and DAPK1. Lastly, in vitro experiment was also conducted on the primary neonatal rat ventricular cardiomyocytes (NRVCMs) to validate the results. Results Mice in the LPS group, as compared to the control group, had lower left ventricular ejection fraction, left ventricular fractional shortening, left ventricular systolic pressure, and ±dp/dt, but a higher left ventricular end-diastolic pressure, while the serum expression of IL-1β, IL-6, TNF-α, and cTn-T was up-regulated evidently with the increased apoptotic index of myocardial tissues. However, miR-141 and Bcl-2/Bax were down-regulated with elevated DAPK1 and cleaved caspase-3. The above changes were ameliorated in mice from the LPS + pre-miR-141 group relative to the LPS group, while those in the LPS + anti-miR-141 group were further deteriorated. In vitro experiment showed that miR-141 overexpression could reduce the apoptosis of LPS-induced NRVCMs and the levels of inflammatory cytokines with the increased cell viability. Conclusion MiR-141 could decrease inflammatory response and reduce myocardial cell apoptosis by targeting DAPK1, thereby playing the promising protective role in SIC.

The targeting of DAPK1 with miR‐190a‐3p promotes autophagy in trophoblast cells

“…Our study found that LC3B and Beclin1 were upregulated and p62 was downregulated after knockdown of DAPK1 in JEG‐3 cells. Lipopolysaccharide‐induced SIC models were constructed to investigate the role and mechanism of miR‐141‐targeted DAPK1 in SIC, which found that miR‐141 could decrease the inflammatory response and reduce the apoptosis of myocardial cells through downregulating the expression of DAPK1 in SIC (Song et al, 2021). Considering the significance of DAPK1 in Alzheimer's disease (AD) and its target relationship with miR‐130a‐3p, Wang et al hypothesized that miR‐130a‐3p could improve cognitive function in AD through targeting DAPK1 (Wang, Shi, et al, 2021).…”