Inhibition of microRNA-23b prevents polymicrobial sepsis-induced cardiac dysfunction by modulating TGIF1 and PTEN

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Sepsis Pathophysiology

Background:

• Sepsis-induced cardiovascular dysfunction is a leading cause of mortality.
• Cardiac fibrosis is a critical factor in sepsis-induced cardiac dysfunction, but its underlying mechanisms remain unclear.
• MicroRNAs (miRNAs) are emerging as key regulators in cardiovascular diseases.

Purpose of the Study:

• To investigate the role of microRNA-23b (miR-23b) in sepsis-induced cardiac fibrosis and dysfunction.
• To elucidate the molecular mechanisms by which miR-23b contributes to cardiac fibrosis.
• To evaluate the therapeutic potential of inhibiting miR-23b in a sepsis model.

Main Methods:

• Cecal ligation and puncture (CLP) model to induce sepsis in vivo.
• Transfection of miR-23b inhibitor in myocardial tissue.
• Assessment of cardiac function, fibrosis, and survival rates.
• Dual-Glo Luciferase assay to confirm miR-23b targets (TGIF1 and PTEN).
• Analysis of TGF-β1/Smad2/3 and AKT/N-Cadherin signaling pathways.

Main Results:

• miR-23b was significantly upregulated in heart tissue during CLP-induced sepsis.
• Inhibition of miR-23b improved survival, cardiac output, and left ventricular systolic function in late sepsis.
• miR-23b inhibition alleviated cardiac fibrosis by suppressing TGF-β1/Smad2/3 and AKT/N-Cadherin signaling.
• TGIF1 and PTEN were identified as direct targets of miR-23b.
• miR-23b blockade restored the balance of pro-fibrotic and anti-fibrotic factors.

Conclusions:

• miR-23b is a critical mediator of cardiac fibrosis and myocardial dysfunction in late sepsis.
• miR-23b promotes cardiac fibrosis by targeting TGIF1 and PTEN, thereby activating TGF-β1/Smad2/3 and AKT/N-Cadherin signaling pathways.
• Blockade of miR-23b represents a promising therapeutic strategy for preventing and treating sepsis-induced cardiac dysfunction.