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Inflammation

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Attenuation of Sepsis-Induced Cardiomyopathy by Regulation of MicroRNA-23b Is Mediated Through Targeting of MyD88-Mediated NF-κB Activation

  • Chao Cao
  • Yan Zhang
  • Yanfen Chai
  • Lijun Wang
  • Chengfen Yin
  • Songtao Shou
  • Heng JinEmail author
ORIGINAL ARTICLE
  • 7 Downloads

Abstract

Myocardial cell injury or cardiomyopathy is associated with excessive inflammatory response and apoptosis of cardiac myocytes during sepsis. MicroRNA-23b (miR-23b) is a multifunctional miRNA that is considered to regulate immunosuppression in sepsis. The aim of this study was to examine the effect of miR-23b on cardiomyopathy induced by sepsis and to explore the potential mechanism involved. Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP), and the level of miR-23b at different time points was measured by quantitative real-time polymerase chain reaction (qPCR). Then, we overexpressed miR-23b in vivo and in vitro. The rats were subjected to CLP 7 days after transfection. Cardiac function, inflammatory response, and heart tissues were examined 3 days thereafter. In an in vitro experiment, H9C2 cardiomyoblasts were stimulated with lipopolysaccharide (LPS) after transfection of miR-23b, following which apoptosis and the level of NF-κB were analyzed. The expression of miR-23b was upregulated during polymicrobial sepsis, and transfection of miR-23b lentivirus improved the outcome of sepsis-induced cardiomyopathy by attenuating inflammatory responses and protecting against histopathological damage. In in vitro experiments, elevated miR-23b inhibited excessive apoptosis of cardiomyocytes, which may be because activation of the NF-κB signaling pathway was inhibited by the decreased levels of TRAF6 and IKKβ. Therefore, miR-23b improved sepsis-induced cardiomyopathy by attenuating the inflammatory response, suppressing apoptosis, and preventing NF-κB activation via targeted inhibition of TRAF6 and IκκB. These results indicated that miR-23b may represent a novel therapeutic approach for clinical treatment of sepsis-induced cardiomyopathy.

KEY WORDS

microRNA-23b sepsis-induced cardiomyopathy inflammatory response NF-κB TRAF6 IκκB 

Abbreviations

BNP

Brain natriuretic peptide

CK-MB

Creatine kinase-MB

CLP

Cecal ligation and puncture

CO

Cardiac output

EF

Ejection fraction

ELISA

Enzyme-linked immunosorbent assay

EMSA

Electrophoretic mobility shift assay

ICAM-1

Intercellular cell adhesion molecule 1

LPS

Lipopolysaccharide

MIF

Migration inhibitory factor

miR-23b

MicroRNA-23b

NF-κB

Nuclear factor kappaB

qPCR

Quantitative real-time polymerase chain reaction

SIC

Sepsis-induced cardiomyopathy

TLR

Toll-like receptor

VCAM-1

Vascular cell adhesion molecule 1

Notes

Authors’ Contributions

CC performed experiments, analyzed data, prepared figures, and wrote the manuscript. YZ, LJW, YFC, and STS performed experiments and analyzed data. CFY performed the histological examination of the heart tissues. HJ designed experiments, analyzed data, prepared figures, and wrote the manuscript. All authors read and approved the final manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81871593 to YFC), Theory E Emergency Medical Research Fund of China (Grant No. R2015026 to CC), and Tianjin Medical University General Hospital Fund of China (Grant No. ZYYFY2015010 to CC, ZYYFY2016026 to YZ).

Compliance with Ethical Standards

Competing Interests

The authors declare that they have no conflicts of interest.

Ethics Approval and Consent to Participate

All experimental manipulations were undertaken in accordance with the Guide for the Care and Use of Medical Laboratory Animals (Ministry of Health, P.R. China, 1998), with the approval of the Scientific Investigation Board, Tianjin Medical University General Hospital, Tianjin, China.

Supplementary material

10753_2019_958_MOESM2_ESM.docx (13 kb)
ESM 1 (DOCX 13 kb)
10753_2019_958_MOESM1_ESM.docx (58 kb)
ESM 2 (DOCX 57 kb)

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Emergency MedicineTianjin Medical University General HospitalTianjinChina
  2. 2.Department of Internal MedicineThe University of Iowa Carver College of MedicineIowa CityUSA
  3. 3.Department of Critical Care MedicineTianjin Third Central HospitalTianjinChina

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