MiR-181-5p protects mice from sepsis via repressing HMGB1 in an experimental model.

OBJECTIVE: Lentivirus-delivered microRNA (miR) has been reported to improve survival outcomes and organ dysfunction. The present study is aimed to explore whether sepsis-associated miR, miR-181-5p, could mitigate sepsis-induced inflammation and organ injury by the lentivirus-expressing system. MATERIALS AND METHODS: Cecal ligation and puncture (CLP)-operated mice were treated with lentivirus-expressing miR-181-5p (miR-agomir) 7 days before surgical operation by intravenous injection. Acute renal and hepatic injuries were assessed using specific biomarkers. Survival outcomes were evaluated following CLP operation within 72 hours. RESULTS: Lentivirus-delivered miR-181-5p improves survival outcomes of CLP-induced septic mice. The rescue of miR-181-5p expression by lentivirus expression vector protects against sepsis-induced renal and hepatic dysfunction. Sepsis-triggered inflammatory response and the release of HMGB1 level could be attenuated by miR-agomir administration. We also found that HMGB1 was a direct target of miR-181-5p, and that the overexpression of miR-81-5p led to a significant decrease in HMGB1 protein expression. CONCLUSIONS: miR-181-5p-mediated protective effects in septic mice were modulated, at least partially, through post-transcriptional repression of HMGB1 protein expression. The findings suggest that miR-181-5p may function as an HMGB1 antagonist for alleviating sepsis-induced systemic inflammatory diseases.