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MiRNA-133a aggravates inflammatory responses in sepsis by targeting SIRT1
Lei Chen1, Wenfeng Xie2, Lichun Wang1
1Department of Intensive Care Unit, The Sixth Affiliated Hospital of Sun Yat-sen University, 510655 Guangzhou, Guangdong, China.
Background:
Sepsis is a systemic inflammatory response syndrome. MicroRNA (miRNA) plays an important role in immune cell activation, inflammatory cytokine release and immune response. However, the mechanism of miR-133a in sepsis remains largely unknown.
Methods:
Sepsis mice models were established by applying the cecal ligation and puncture (CLP) method. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to detect the relative expression of miR-133a and inflammatory cytokines. Hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (Elisa) were used to evaluate organ injury and inflammatory response. Besides, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used to construct sepsis cell models. Further, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out to confirm the relationship between miR-133a and sirtuin-1 (SIRT1). In addition, western blot (WB) assay was performed to measure the relative SIRT1 protein level.
Results:
MiR-133a was highly expressed in sepsis patients and CLP mice models. Knockdown of miR-133a inhibited sepsis-induced lung, liver and kidney injuries and inflammatory response in CLP mice models. Besides, miR-133a inhibitor also alleviated the inflammatory response of RAW264.7 macrophages induced by LPS. SIRT1 was a target of miR-133a, and silenced SIRT1 could reverse the anti-inflammatory effect of miR-133a inhibitor on LPS-induced sepsis cell models.
Conclusion:
MiR-133a promoted the inflammatory response of sepsis by inhibiting the expression of SIRT1, which might provide a new therapeutic strategy for sepsis.
Insights
MicroRNA-133a (miR-133a) exacerbates sepsis by suppressing SIRT1. Inhibiting miR-133a reduces organ damage and inflammation, offering a potential new therapeutic strategy for sepsis.
Area of Science:
- Immunology
- Molecular Biology
- Pathophysiology
Background:
- Sepsis is a life-threatening systemic inflammatory response.
- MicroRNAs (miRNAs) are crucial regulators of immune responses, but miR-133a's role in sepsis is unclear.
- Understanding miR-133a's mechanism is vital for developing novel sepsis therapies.
Purpose of the Study:
- To investigate the role and mechanism of miR-133a in sepsis.
- To determine the relationship between miR-133a and sirtuin-1 (SIRT1) in sepsis.
- To evaluate miR-133a as a potential therapeutic target for sepsis.
Main Methods:
- Cecal ligation and puncture (CLP) in mice and lipopolysaccharide (LPS)-induced macrophages established sepsis models.
- Quantitative real-time PCR (qRT-PCR), H&E staining, and ELISA assessed miR-133a, cytokine levels, and organ injury.
- Dual-luciferase reporter, RNA immunoprecipitation (RIP), and Western blot (WB) assays elucidated the miR-133a-SIRT1 interaction.
Main Results:
- miR-133a expression was significantly upregulated in sepsis patients and mouse models.
- miR-133a knockdown ameliorated sepsis-induced lung, liver, and kidney injuries and inflammation.
- miR-133a inhibition suppressed LPS-induced inflammatory responses in macrophages, an effect reversed by SIRT1 silencing.
Conclusions:
- miR-133a promotes sepsis-related inflammation by inhibiting SIRT1 expression.
- Targeting miR-133a presents a promising therapeutic strategy for sepsis.
- The miR-133a/SIRT1 axis is a key player in sepsis pathogenesis.
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