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Induction of an Inflammatory Response in Primary Hepatocyte Cultures from Mice
Published on: March 10, 2017
MicroRNA-21 Contributes to Acute Liver Injury in LPS-Induced Sepsis Mice by Inhibiting PPARα Expression
Xianjin Du1, Miao Wu2, Dan Tian2
1Department of Critical Care Medicine, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, Hubei 430060, China.
Abstract:
The severity of sepsis may be associated with excessive inflammation, thus leading to acute liver injury. MicroRNA-21 is highly expressed in the liver of a variety of inflammation-related diseases, and PPARα is also proved to participate in regulating inflammation. In the present study, the LPS-induced sepsis model was established. We found that microRNA-21 expression was upregulated in the liver of sepsis mice, and microRNA-21 inhibition significantly reduced the liver injury. The expression of liver injury markers, inflammation cytokines, and PPARα in the septic mice was higher than in antagomir-21 treated septic mice. In addition, we also found that PPARα is the target gene of microRNA-21; PPARα antagonist GW6471 could reverse the effect of antagomir-21. In conclusion, our study illustrated that microRNA-21 exacerbate acute liver injury in sepsis mice by inhibiting PPARα expression.
Insights
MicroRNA-21 inhibition protects against sepsis-induced acute liver injury by reducing inflammation. This study shows microRNA-21 exacerbates liver damage by suppressing PPAR-alpha expression in mice.
Area of Science:
- Biomedical Science
- Molecular Biology
- Pathology
Background:
- Sepsis severity correlates with excessive inflammation, potentially causing acute liver injury.
- MicroRNA-21 is upregulated in inflammatory liver diseases.
- Peroxisome proliferator-activated receptor alpha (PPARα) plays a role in inflammation regulation.
Purpose of the Study:
- To investigate the role of microRNA-21 in lipopolysaccharide (LPS)-induced sepsis and associated acute liver injury.
- To elucidate the mechanism by which microRNA-21 affects liver injury in sepsis, focusing on its relationship with PPARα.
Main Methods:
- Establishment of a lipopolysaccharide (LPS)-induced sepsis mouse model.
- Analysis of microRNA-21 expression in liver tissues.
- Assessment of liver injury markers and inflammatory cytokines.
- Investigation of PPARα expression and its regulation by microRNA-21 using antagonists.
Main Results:
- MicroRNA-21 expression was significantly upregulated in the livers of sepsis mice.
- Inhibition of microRNA-21 (using antagomir-21) markedly reduced liver injury and inflammation.
- Sepsis mice exhibited higher levels of liver injury markers, inflammatory cytokines, and PPARα compared to antagomir-21 treated mice.
- PPARα was identified as a direct target gene of microRNA-21, and its antagonist (GW6471) reversed the protective effects of antagomir-21.
Conclusions:
- MicroRNA-21 exacerbates acute liver injury in sepsis by inhibiting PPARα expression.
- Targeting microRNA-21 presents a potential therapeutic strategy for sepsis-induced liver injury.
