International Immunopharmacology Volume 88, November 2020, 106848

MiRNA-133a aggravates inflammatory responses in sepsis by targeting SIRT1

Author links open overlay panelLeiChenaWenfengXiebLichunWangaXiaofeiZhangaEnheLiuaQiuyeKoua

Department of Intensive Care Unit, The Sixth Affiliated Hospital of Sun Yat-sen University, 510655 Guangzhou, Guangdong, ChinabDepartment of Intensive Care Unit, The First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, Guangdong, China

Received 18 February 2020, Revised 17 July 2020, Accepted 26 July 2020, Available online 7 August 2020.

Abstract

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.

Keywords

SepsismiR-133aSIRT1CLP mice modelsInflammatory response

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