MicroRNA-21 Contributes to Acute Liver Injury in LPS-Induced Sepsis Mice by Inhibiting PPARα Expression.

Xianjin Du,Lu Wang,Liying Zhan,Jianlin Zhou,Miao Wu,Dan Tian,Xiao-Jie Lu

doi:10.1155/2020/6633022

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.

Highlights

Sepsis is a common cause of death in intensive care units [1]
This study illustrated that miR-21 suppression attenuated liver injury in LPS-induced sepsis mice, by potentiating PPARα expression, which suggested a contribution of miR21 in the pathogenesis of sepsis-induced liver injury
AntagomiR-21 and PPARα represented antiinflammatory activities in septic mice. These findings demonstrated that the miR-21/PPARα pathway might serve as a potential target in sepsis therapy

Summary

Introduction

Sepsis is a common cause of death in intensive care units [1]. It is a public health problem worldwide, and approximately 19 million people suffer from sepsis yearly [2]. Sepsis was defined as a “life-threatening organ dysfunction caused by a deregulated host response to infection” at the Sepsis-3 conference [3]. The acute liver injury occurs at any stage of sepsis; the dysregulation of hepatocyte function may be related to cytokine storm [4]. Liver injury can aggravate the development of the disease and lead to death [5]. Understanding the pathogenesis of sepsis is very important for the treatment of sepsis

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