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Published on: April 11, 2012
miR-103a-3p Could Attenuate Sepsis-Induced Liver Injury by Targeting HMGB1
Leifeng Chen1, Qiang Lu2, Fumou Deng2
1Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China.
Abstract:
The liver is one of the most vulnerable organs during sepsis. Current studies have proven that microRNAs play important roles in injury and inflammation. The current study aimed to investigate the role of miR-103 in septic liver injury. The sepsis model was established by cecal ligation and puncture in mice. Then, the mice were divided into four groups: normal group, sepsis group, sepsis + miR-103a-3p agomir group, and sepsis + negative control group. Liver injury was observed by hematoxylin-eosin staining and electron microscopic studies. The sepsis-induced apoptosis in liver tissues was assessed by TUNEL staining. The levels of inflammatory cytokines in liver tissues were determined by enzyme-linked immunosorbent assay kits. The targeted gene of miR-103a-3p in cells was predicted by bioinformatics algorithm and confirmed by dual-luciferase reporter assay. The expression of miR-103a-3p, HMBG1, and the apoptosis-relative proteins was examined by quantitative real-time polymerase chain reaction and Western blotting. miR-103a-3p was downregulated in liver tissues of sepsis animals. miR-103a-3p agomir could alleviate liver injury including the tissue injury and mitochondrial damage, inhibit the secretion of inflammatory factors, and decrease the apoptosis of liver cells. The high-mobility group B1 (HMGB1) was overregulated in sepsis, and it was a downstream target gene of miR-103a-3p. The results of the rescue assay confirmed that miR-103a-3p had a protection role in septic liver injury by targeting HMGB1. In summary, HMGB1 was one of the genes targeted by miR-103a-3p, which played roles in septic injury. These data may provide novel insight for the identification of new target and treatment strategies for septic liver injury.
Insights
MicroRNA-103a-3p (miR-103a-3p) protects against septic liver injury by downregulating high-mobility group B1 (HMGB1). Restoring miR-103a-3p levels alleviates liver damage and inflammation during sepsis.
Area of Science:
- Hepatology
- Molecular Biology
- Sepsis Research
Background:
- Sepsis poses a significant threat to liver function, leading to severe injury.
- MicroRNAs (miRNAs) are implicated in regulating inflammatory responses and cellular damage during sepsis.
- The specific role of miR-103 in septic liver injury requires further elucidation.
Purpose of the Study:
- To investigate the role of miR-103a-3p in the pathogenesis of septic liver injury.
- To determine the therapeutic potential of modulating miR-103a-3p levels in a mouse model of sepsis.
- To identify the molecular targets of miR-103a-3p involved in septic liver injury.
Main Methods:
- A mouse model of sepsis was induced via cecal ligation and puncture.
- Liver injury was assessed using histological and ultrastructural analyses.
- Apoptosis, inflammatory cytokine levels, and protein expression were quantified using TUNEL, ELISA, qRT-PCR, and Western blotting.
- Bioinformatics and dual-luciferase reporter assays identified high-mobility group B1 (HMGB1) as a direct target of miR-103a-3p.
Main Results:
- miR-103a-3p expression was significantly downregulated in the livers of septic mice.
- Administration of miR-103a-3p agomir attenuated liver tissue damage, reduced mitochondrial injury, and decreased hepatocyte apoptosis.
- miR-103a-3p agomir treatment suppressed the release of key inflammatory cytokines.
- HMGB1 was found to be upregulated in sepsis and confirmed as a direct downstream target of miR-103a-3p.
Conclusions:
- miR-103a-3p plays a protective role in septic liver injury.
- The protective mechanism involves the downregulation of HMGB1, a key mediator of sepsis-induced inflammation and injury.
- Modulating miR-103a-3p represents a potential therapeutic strategy for managing septic liver injury.
