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

Area of Science:

• Molecular Biology
• Cardiovascular Research
• Sepsis Pathophysiology

Background:

• MicroRNAs (miRNAs) are key regulators of protein translation.
• The precise role of miR-181b in sepsis-induced myocardial injury remains unclear.
• High-mobility group box-1 protein (HMGB1) is implicated in inflammatory responses during sepsis.

Purpose of the Study:

• To elucidate the mechanism of miR-181b in regulating inflammatory responses in sepsis-induced myocardial injury.
• To investigate the direct targeting of high-mobility group box-1 protein (HMGB1) by miR-181b.
• To assess the therapeutic potential of modulating miR-181b/HMGB1 interaction in sepsis.

Main Methods:

• Establishment of a rat model of sepsis using cecal ligation and puncture (CLP).
• Investigation of miR-181b and HMGB1 expression effects on cardiomyocytes.
• Bioinformatics analysis and dual-luciferase reporter gene assay to confirm miR-181b targeting of HMGB1.
• RT-qPCR, western blot, and TUNEL assay to evaluate gene expression and cardiomyocyte apoptosis.

Main Results:

• Sepsis significantly increased HMGB1 expression and inflammatory factors in myocardial tissue.
• Overexpression of miR-181b improved cardiomyocyte morphology and reduced inflammatory cell infiltration.
• miR-181b directly targets HMGB1, and HMGB1 downregulation mitigated inflammatory factors and cardiomyocyte apoptosis in sepsis.

Conclusions:

• miR-181b exerts protective effects against sepsis-induced myocardial injury by downregulating HMGB1.
• The miR-181b/HMGB1 axis represents a critical pathway in sepsis-related inflammation and cardiac damage.
• Targeting the miR-181b/HMGB1 interaction may offer novel therapeutic strategies for managing sepsis.