MicroRNA-381-3p signatures as a diagnostic marker in patients with sepsis and modulates sepsis-steered cardiac damage and inflammation by binding HMGB1

• Published in: Bioengineered 2021-12, Vol.12 (2), p.11936-11946
• Main Authors: Liu, Jian, Yang, Yadong, Lu, Rong, Liu, Qin, Hong, Shukun, Zhang, Zhaolong, Hu, Guoxin
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biomarkers - metabolism; Cardiotonic Agents - metabolism; Case-Control Studies; Cell Line; Female; Gene Expression Regulation; HMGB1; HMGB1 Protein - metabolism; Humans; inflammation; Inflammation - complications; Inflammation - genetics; Male; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; MiR-381-3p; myocardial dysfunction; Myocardium - pathology; Protein Binding; Rats; Rats, Sprague-Dawley; Research Paper; sepsis; Sepsis - complications; Sepsis - diagnosis; Sepsis - genetics; Sepsis - pathology; viability
• ISSN: 2165-5979; 2165-5987
• DOI: 10.1080/21655979.2021.2006967

Immune response imbalance and cardiac dysfunction caused by sepsis are the main reasons for death in sepsis. This study aimed to confirm the expression and diagnostic possibility of microRNA-381-3p (miR-381-3p) and its mechanism in sepsis. Quantitative real-time PCR (qRT-PCR) and receiver operating characteristic (ROC) were used to reveal the levels and clinical significance of miR-381-3p. Pearson correlation was conducted to provide the correlations between miR-381-3p and several indexes of sepsis. The H9c2 cell models were constructed by lipopolysaccharide (LPS), and cecal ligation and puncture (CLP) was applied to establish the Sprague-Dawley (SD) rat models. Cell Counting Kit-8 (CCK-8) and flow cytometry were the methods to detect the cell viability and death rate of H9c2. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the concentration of inflammatory cytokines. The target gene of miR-381-3p was validated via the luciferase report system. The low expression of miR-381-3p was found in the serum of patients with sepsis. The lessened miR-381-3p could be a marker in the discrimination of sepsis patients. Overexpression of miR-381-3p could repress the mRNA expression of HMGB1, inhibit the cell apoptosis and inflammatory response, and motivate the viability of sepsis cells. At the same time, enhanced miR-381-3p promoted the inhibition of inflammation and cardiac dysfunction in the rat model of sepsis. Collectively, reduced levels of serum miR-381-3p can be used as an index to detect sepsis patients. MiR-381-3p restored the inflammatory response and myocardial dysfunction caused by sepsis via HMGB1.