MicroRNA-193-3p attenuates myocardial injury of mice with sepsis via STAT3/HMGB1 axis

Jianyuan Pan,Laeuf Ilona Mariya Christoph,Buse Alexan,Yongqin Tang,Chiristine Bettina,Dorn Dennis

doi:10.1186/s12967-021-03022-x

Abstract

ObjectiveLittle is known regarding the functional role of microRNA-193-3p (miR-193-3p) in sepsis. Hence, the aim of the present study was to investigate the effect of miR-193-3p on myocardial injury in mice with sepsis and its mechanism through the regulation of signal transducers and activators of transcription 3 (STAT3).MethodsThe mice model of sepsis was established by cecal ligation and puncture (CLP), septic mice were injected with miR-193-3p agomir, miR-193-3p antagomir or siRNA-STAT3. The expression of miR-193-3p, STAT3 and HMGB1 in the myocardial tissue of septic mice were detected. Cardiac ultrasound, hemodynamics, myocardial injury markers, inflammatory factors and cardiomyocyte apoptosis in septic mice were measured.ResultsMiR-193-3p expression was reduced while STAT3 expression was increased in septic mice. Down-regulated STAT3 or up-regulated miR-193-3p improved cardiac function, attenuated myocardial injury, inflammation and cardiomyocyte apoptosis in septic mice. Knockdown STAT3 reversed the role of inhibited miR-193-3p for mice with sepsis. miR-193-3p targeted STAT3, thereby inhibiting HMGB1 expression.ConclusionThis study provides evidence that miR-193-3p targets STAT3 expression to reduce HMGB1 expression, thereby reducing septic myocardial damage. MiR-193-3p might be a potential candidate marker and therapeutic target for sepsis.

Highlights

Sepsis is a serious clinical symptom induced by a deregulated systemic host response to infection contributing to tissue damage and organ dysfunction [1]
MiR‐193‐3p expression is reduced in myocardial tissues of mice with sepsis To explore the effect of miR-193-3p on myocardial injury in septic mice, we constructed a sepsis mouse model and used cardiac ultrasound, hemodynamics and measurements of serum factors to identify the model
It was found that in relation to the sham group, LVIDs and Heart rate (HR) level enhanced while FS, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), + dp/dt max, − dp/dt max and mean arterial pressure (MAP) level depressed in the cecal ligation and puncture (CLP) group (Fig. 1A–F)

Summary

Introduction

Sepsis is a serious clinical symptom induced by a deregulated systemic host response to infection contributing to tissue damage and organ dysfunction [1]. It is one of the main causes of infection death and intensive care unit death, and the prognosis has not ameliorated dramatically in the past few years [2]. A study has reported that overexpression of miR-135a can increase inflammation and myocardial dysfunction induce by sepsis [13]. Another study has revealed that miR-23b mediates the activation of cardiac fibrosis of late sepsis myocardial dysfunction [14]. We speculated that miR193-3p could regulate the uncontrolled inflammatory response in sepsis via modulating STAT3

Methods

Results

Conclusion