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Updated: Dec 7, 2025
Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
Published on: February 9, 2014
SP1-induced ZFAS1 aggravates sepsis-induced cardiac dysfunction via miR-590-3p/NLRP3-mediated autophagy and
Jing-Jing Liu1, Yong Li2, Ming-Shi Yang1
1Department of Intensive Care Medicine, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan Province, PR China.
Insights
Zinc finger antisense 1 (ZFAS1) aggravates sepsis-induced cardiac dysfunction by targeting miR-590-3p, impacting autophagy and pyroptosis. Inhibiting ZFAS1 may offer a therapeutic strategy for sepsis complications.
Area of Science:
- Cardiology
- Molecular Biology
- Cellular Biology
Background:
- Sepsis-induced cardiac dysfunction is a major cause of mortality in septic patients.
- Autophagy and pyroptosis are implicated in the pathogenesis of septic cardiac dysfunction.
- The role of zinc finger antisense 1 (ZFAS1) in sepsis-induced myocardial dysfunction requires further investigation.
Purpose of the Study:
- To investigate the impact of ZFAS1 on sepsis-induced myocardial dysfunction.
- To elucidate the regulatory mechanisms involving pyroptosis and autophagy in this process.
- To determine the role of ZFAS1 in sepsis-induced cardiac dysfunction.
Main Methods:
- Sepsis models were established in vivo (cecal ligation and puncture) and in vitro (lipopolysaccharide-stimulated cardiomyocytes).
- Myocardial injury, pyroptosis, and autophagy were assessed using histological, biochemical, and molecular techniques.
- The regulatory interactions between SP1, ZFAS1, miR-590-3p, and the AMPK/mTOR signaling pathway were investigated.
Main Results:
- ZFAS1 was highly expressed in sepsis-induced cardiac dysfunction models.
- Knockdown of ZFAS1 reduced pyroptosis and attenuated autophagy inhibition.
- SP1 positively regulated ZFAS1 expression, and miR-590-3p acted as a downstream effector, reversing ZFAS1-mediated dysfunction via the AMPK/mTOR pathway.
Conclusions:
- ZFAS1, activated by SP1, exacerbates sepsis-induced cardiac dysfunction.
- The ZFAS1/miR-590-3p axis regulates cardiomyocyte autophagy and pyroptosis through the AMPK/mTOR signaling pathway.
- Targeting ZFAS1 may represent a therapeutic approach for sepsis-induced cardiac dysfunction.
Background:
Sepsis-induced cardiac dysfunction is one of the leading complications of sepsis, contributing to the high morbidity and mortality of septic patients. Several lines of evidence have demonstrated that autophagy and pyroptosis may be involved in septic cardiac dysfunction. In this study, we examined the impact of zinc finger antisense 1 (ZFAS1) on sepsis-induced myocardial dysfunction via regulating pyroptosis and autophagy.
Method:
Mice with cecal ligation and puncture (CLP)-induced sepsis was constructed in vivo. Myocardial injury was assessed by H&E staining, immunohistochemistry (IHC) for NLRP3, caspase 1, and interleukin (IL)-1β, as well as ELISA assay for serum levels of creatine kinase (CK), CK-MB, tumor necrosis factor α (TNF-α), and IL-1β. Primary cardiomyocytes exposed to lipopolysaccharide (LPS) were established to simulate sepsis-induced cardiac dysfunction in vitro. Cell viability was examined by MTT assay and concentration of TNF-α and IL-1β was measured by ELISA. Flow cytometry, immunofluorescent staining and western blotting were performed to assess pyroptosis and autophagy. The transcriptional regulation of SP1 on ZFAS1 was determined using ChIP assay. Luciferase reporter assay was performed to verify the ZFAS1/miR-590-3p interaction. Besides, activation of AMPK/mTOR signaling was detected using western blotting.
Results:
Highly expressed ZFAS1 was observed in sepsis-induced cardiac dysfunction in the in vivo and in vitro model. Knockdown of ZFAS1 robustly abolished LPS-induced pyroptosis and attenuated the inhibition of autophagy. SP1 was identified to be an essential transcription factor to positively regulate ZFAS1 expression. Moreover, miR-590-3p functioned as a downstream effector to reverse ZFAS1-mediated sepsis-induced cardiac dysfunction. AMPK/mTOR signaling was involved in miR-590-3p-regulated autophagy and pyroptosis of cardiomyocytes. Furthermore, the regulatory network of ZFAS1/miR-590-3p on AMPK/mTOR signaling was verified in vivo.
Conclusion:
ZFAS1, activated by SP1, aggravates the progression of sepsis-induced cardiac dysfunction via targeting miR-590-3p/AMPK/mTOR signaling-mediated autophagy and pyroptosis of cardiomyocytes.
