MiR-25 inhibits sepsis-induced cardiomyocyte apoptosis by targetting PTEN.

Yulong Yao,Fangyuan Sun,Ming Lei

doi:10.1042/bsr20171511

Yulong Yao, Fangyuan Sun + Show 1 more

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https://doi.org/10.1042/bsr20171511

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Journal: Bioscience reports	Publication Date: Apr 13, 2018
Citations: 52	License type: CC BY 4.0

Affiliation: Seventh People's Hospital of Shanghai

Abstract

To investigate the regulatory mechanism of miR-25 in sepsis-induced cardiomyocyte apoptosis. Rats models of sepsis were established by cecal ligation and puncture (CLP). Lipopolysaccharide (LPS)-induced cardiomyocyte was used as an in vitro model of sepsis. The expressions of miR-25, tensin homolog deleted on chromosome 10 (PTEN), Toll-like receptors 4 (TLR4), and p-p65 were analyzed by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by ELISA. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated d-UTP nick end labeling (TUNEL) assay. The relationship between miR-25 and PTEN was measured by luciferase reporter assays. MiR-25 expression in serum of CLP rats and LPS-induced cardiomyocyte was decreased, while the contents of TNF-α and IL-6 were increased. Moreover, the expressions of PTEN, TLR4, and p-p65 in LPS-induced cardiomyocyte were significantly increased. Overexpression of miR-25 increased the survival rate of rats, inhibited LPS-increased cardiomyocyte apoptosis, reversed the increased expression of PTEN, TLR4, p-p65, TNF-α, and IL-6 induced by LPS. The luciferase assay demonstrated that PTEN was a target of miR-25. Additionally, pcDNA-PTEN reversed the inhibitory effect of miR-25 mimic on cardiomyocyte apoptosis, while TAK-242 (TLR-4 inhibitor) countered this effect. miR-25 reduced LPS-induced cardiomyocyte apoptosis by down-regulating PTEN/TLR4/NF-κB axis.

Highlights

Sepsis, an infection-induced systemic inflammatory disorder, can lead to multiple organ dysfunction syndrome [1]
MiR-25 has been found as an inhibitor for cardiomyocyte apoptosis induced by hypoxia/re-oxygenation [7], which suggest that miR-25 may be related to myocardial function
It was reported that the mortality rate of septic patients with myocardial dysfunction was 70%, and the mortality rate of septic patients without myocardial dysfunction was only 20% [15]

Summary

Introduction

An infection-induced systemic inflammatory disorder, can lead to multiple organ dysfunction syndrome [1]. Some results have been achieved in the prevention and treatment of sepsis in recent years, sepsis remains the main cause of mortality in the intensive care unit (ICU) [2,3]. Sepsis-induced myocardial dysfunction (SIMD) is one of the reasons leading to increased mortality in sepsis, but the pathogenesis remains unclear. It is important to explore its pathogenesis in the diagnosis, prevention, and treatment of sepsis. Wang et al [5] found that miR-21-3p could promote myocardial injury induced by sepsis. Zhou et al [6] reported that miR-155 alleviated myocardial injury in septic rats by inhibiting JNK-related inflammatory signaling. Whether miR-25 is involved in the pathogenesis of SIMD remains unknown

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