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MicroRNA-181b Inhibits Inflammatory Response and Reduces Myocardial Injury in Sepsis by Downregulating HMGB1

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Abstract

MicroRNAs (miRNAs) are short endogenous noncoding RNAs regulating protein translation. However, the specific mechanism by which miR-181b influences sepsis via high-mobility group box-1 protein (HMGB1) still remains unknown. Thus, the aim of this study is to investigate the mechanism of miR-181b in regulating inflammatory response in sepsis-induced myocardial injury through targeting high-mobility group box-1 protein (HMGB1). Through cecal ligation and puncture (CLP), the rat model of sepsis was established. Then, the effect of altered expression of miR-181b and HMGB1 on cardiomyocytes was investigated. The positive expression rate of HMGB1, concentration of inflammatory factors, and serum myocardial enzyme of myocardial tissues were determined. Besides, the binding site between miR-181b and HMGB1 was determined by bioinformatics information and dual-luciferase reporter gene assay. The expression of related genes in cells of each group was determined by RT-qPCR and western blot analysis, and the apoptosis rate of transfected cells in each group was determined by TUNEL assay. HMGB1 expression and inflammatory factors were significantly increased in myocardial tissue of rats with sepsis. Cell morphology and the infiltration of inflammatory cells were significantly improved by overexpression of miR-181b. miR-181b directly targeted HMGB1, and downregulation of HMGB1 reduced inflammatory factors and myocardial injury and inhibited cardiomyocyte apoptosis in sepsis. This present study suggests that miR-181b decreased inflammatory factors and reduced myocardial injury in sepsis through downregulation of HMGB1. Thus, a better understanding of this process may aid in the development of novel therapeutic agents in sepsis.

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Acknowledgments

We acknowledge and appreciate our colleagues for their valuable efforts and comments on this paper.

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Author notes

  1. Lan Ling and Haifeng Wang contributed equally to the work.

Authors and Affiliations

  1. Emergency Department, China-Japan Friendship Hospital, No. 2, Yinghua East Street, Chaoyang District, Beijing, 100029, People’s Republic of China

    Lan Ling, Lida Zhi, Yihuan Deng & Chengdong Gu

  2. Department of Nephropathy, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China

    Haifeng Wang

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  1. Lan Ling
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  2. Lida Zhi
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  4. Yihuan Deng
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  5. Chengdong Gu
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Contributions

Lida Zhi, Haifeng Wang, and Lan Ling designed the study. Yihuan Deng, Chengdong Gu, and Lan Ling collated the data, designed and developed the database, carried out data analyses, and produced the initial draft of the manuscript. Lan Ling contributed to drafting the manuscript. All authors participated in the revised manuscript, and have read and approved the final submitted manuscript.

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Correspondence to Chengdong Gu.

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Ling, L., Zhi, L., Wang, H. et al. MicroRNA-181b Inhibits Inflammatory Response and Reduces Myocardial Injury in Sepsis by Downregulating HMGB1. Inflammation 44, 1263–1273 (2021). https://doi.org/10.1007/s10753-020-01411-w

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  • DOI: https://doi.org/10.1007/s10753-020-01411-w

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