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Updated: Aug 27, 2025

Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
Published on: February 9, 2014
circVMA21 combining with TAF15 stabilizes SOCS3 mRNA to relieve septic lung injury through regulating NF-κB
Zi-Gui Zhu1, Gu-Qing Liao1, Jian-Xin Zhang2
1Department of Intensive Care Unit, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang 421002, Hunan Province, PR China.
Background:
Lung injury is a severe complication of sepsis, which brings great threats and challenges to human health. CircVMA21 has exhibited powerful anti- inflammation capacity. However, its underlying molecule mechanism remains blurry.
Methods:
Lipopolysaccharide (LPS) was used to treat mice and WI-38 cells to establish models of lung injury caused by sepsis. Lung injury was evaluated using HE staining. Cell apoptosis was tested by TUNEL and flow cytometry. Levels of inflammatory cytokines were detected using ELISA assay. CircVMA21 and SOCS3 expression was measured using RT-qPCR. The ROS, MDA, SOD and GSH production were monitored by commercial kits. The protein expression was examined with western blot. The correlations among circVMA21, SOCS3 and TAF15 were confirmed using RIP and RNA-pull down.
Results:
The expression of circVMA21 and SOCS3 was downregulated in LPS-induced lung injury of mice and WI-38 cells. Overexpressing circVMA21 or SOCS3 assuaged LPS-induced cell injury through repressing the levels of inflammatory factors, oxidative stress and cell apoptosis. NF-κB signaling pathway was inactivated by circVMA21 or SOCS3 overexpression. circVMA21 enhanced the stabilization of SOCS3 mRNA via interplaying with TAF15. SOCS3 knockdown destroyed the beneficial impacts of circVMA21 overexpression on LPS-induced cell injury.
Conclusion:
CircVMA21 suppressed LPS-induced the levels of inflammatory factors, oxidative stress and cell apoptosis and improved LPS-induced lung injury by mediating TAF15/SOCS3/NF-κB axis.
Insights
Circular RNA VMA21 (CircVMA21) protects against sepsis-induced lung injury by regulating the TAF15/SOCS3/NF-κB pathway. This study clarifies the molecular mechanism of CircVMA21 in mitigating inflammation and oxidative stress.
Area of Science:
- Biomedical Science
- Molecular Biology
- Sepsis Research
Background:
- Sepsis-induced lung injury poses significant health risks.
- Circular RNA VMA21 (CircVMA21) shows anti-inflammatory potential, but its mechanism is unclear.
Purpose of the Study:
- To elucidate the molecular mechanism of CircVMA21 in sepsis-induced lung injury.
- To investigate the role of CircVMA21 in regulating inflammatory responses and oxidative stress.
Main Methods:
- Established sepsis-induced lung injury models in mice and WI-38 cells using lipopolysaccharide (LPS).
- Assessed lung injury, apoptosis, inflammatory cytokines, oxidative stress markers, and protein expression.
- Utilized RT-qPCR, ELISA, western blot, RIP, and RNA-pull down assays to analyze molecular interactions and expression levels.
Main Results:
- CircVMA21 and SOCS3 expression were downregulated in LPS-induced lung injury.
- Overexpression of CircVMA21 or SOCS3 alleviated LPS-induced injury by reducing inflammation, oxidative stress, and apoptosis.
- CircVMA21 stabilized SOCS3 mRNA via TAF15, inactivating the NF-κB pathway.
Conclusions:
- CircVMA21 mitigates sepsis-induced lung injury by suppressing inflammation, oxidative stress, and apoptosis.
- The protective effect is mediated through the TAF15/SOCS3/NF-κB signaling axis.
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