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Updated: Dec 6, 2025
Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
Published on: April 11, 2012
MiR-181-5p protects mice from sepsis via repressing HMGB1 in an experimental model
1Emergency Center, Lanzhou University Second Hospital, Lanzhou, Gansu Province, China. wintain2017@aliyun.com.
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.
Insights
Lentivirus-delivered microRNA-181-5p (miR-181-5p) protects against sepsis-induced organ injury and improves survival in mice. This protective effect is mediated by downregulating HMGB1, a key inflammatory protein.
Area of Science:
- Molecular Biology
- Immunology
- Sepsis Research
Background:
- MicroRNAs (miRNAs) play crucial roles in regulating gene expression.
- Lentivirus-delivered miRNAs have shown potential in therapeutic applications.
- Sepsis is a life-threatening condition characterized by dysregulated inflammation and organ dysfunction.
Purpose of the Study:
- To investigate the therapeutic potential of miR-181-5p delivered via lentivirus in a mouse model of sepsis.
- To determine if miR-181-5p can mitigate sepsis-induced inflammation and organ injury.
- To elucidate the molecular mechanism underlying miR-181-5p's protective effects.
Main Methods:
- A mouse model of sepsis was established using cecal ligation and puncture (CLP).
- Mice were treated with lentivirus-expressing miR-181-5p (miR-agomir) via intravenous injection prior to CLP.
- Renal and hepatic injuries were assessed using biomarkers, and survival outcomes were monitored.
Main Results:
- Lentivirus-delivered miR-181-5p significantly improved survival rates in septic mice.
- miR-181-5p administration protected against sepsis-induced renal and hepatic dysfunction.
- Sepsis-induced inflammation and HMGB1 levels were reduced by miR-agomir treatment.
- HMGB1 was identified as a direct target of miR-181-5p, with its expression decreased upon miR-181-5p overexpression.
Conclusions:
- miR-181-5p, delivered by lentivirus, confers protection against sepsis-induced organ injury and mortality.
- The protective mechanism involves the post-transcriptional repression of HMGB1.
- miR-181-5p acts as an HMGB1 antagonist, offering a potential therapeutic strategy for sepsis.
