miR-222-3p targeting MEGF9 exacerbates sepsis-induced myocardial injury.

BACKGROUND: Sepsis-induced myocardial injury (SIMI) commonly occurs as a complication of severe sepsis and septic shock. This research aims to explore the function of miR-222-3p inhibition in SIMI and its possible regulatory mechanisms. METHODS: A rat SIMI model was established using the cecal ligation and puncture method. In vitro experiments were conducted using lipopolysaccharide (LPS) to induce myocardial injury in H9C2 cells. miR-222-3p and MEGF9 expression were determined using qRT-PCR. Myocardial injury, inflammatory response, and oxidative stress indicators were detected using the ELISA and biochemical colorimetric assays. Cell viability and apoptosis were assessed using the CCK-8 method and flow cytometry. The interaction between miR-222-3p and MEGF9 was verified through a luciferase reporter gene assay. RESULTS: In the serum of rats with sepsis and LPS-induced H9C2 cells, miR-222-3p exhibited high expression, while MEGF9 was lowly expressed. Inhibition of miR-222-3p alleviated myocardial injury, inflammatory response, and oxidative stress in sepsis rats and LPS-induced cells, as evidenced by reduced CK-MB, cTnI, LDH, IL-6, IL-1β, TNF-α, and MDA level, and enhanced SOD activity. Inhibition of miR-222-3p increased LPS-induced cell viability and diminished apoptosis. miR-222-3p targeted MEGF9. Inhibiting MEGF9 expression could reverse the protective role of miR-222-3p suppression on LPS-induced myocardial injury. CONCLUSION: This study's results indicate that miR-222-3p exacerbates SIMI reactions by targeting and inhibiting MEGF9 expression. It is possible that miR-222-3p functions as a potential therapeutic target for SIMI.