MiR-199a-5p Exacerbated Intestinal Barrier Dysfunction through Inhibiting Surfactant Protein D and Activating NF-κB Pathway in Sepsis.

Xianjin Du,Peng Hu,Jie Wei,Xu Wu,Dan Tian,Chen Yan,Zhanyong Zhu,Wenbin Yang

doi:10.1155/2020/8275026

Xianjin Du, Peng Hu + Show 6 more

Open Access

https://doi.org/10.1155/2020/8275026

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Journal: Mediators of inflammation	Publication Date: May 18, 2020
Citations: 9	License type: CC BY 4.0

Affiliation: Renmin Hospital of Wuhan University

Abstract

Sepsis is a severe disease, which results from the excessive inflammatory response to the infection. Dysfunction of intestinal barrier is a crucial problem in various pathological conditions. Meanwhile, microRNAs exhibit significant roles in the modulation of many diseases, including sepsis. Multiple investigations indicate that miR-199a-5p participates in different human diseases. Nevertheless, little is known on the roles of miR-199a-5p in sepsis. Herein, we evaluated the mechanism of miR-199a-5p on the intestinal barrier dysfunction in sepsis. Intestinal mucosa permeability indicators including D-lactic acid, DAO, and FD-40 levels were determined, and they were greatly increased in sepsis. Then, we proved that miR-199a-5p was induced in sepsis mice tissues and isolated intestinal epithelial cells. Moreover, miR-199a-5p increased D-lactic acid, DAO, and FD-40 while inhibition of miR-199a-5p exhibited a reversed process. Additionally, we observed that miR-199a-5p affected the oxidative damage and inflammation in the intestine tissues from sepsis mice. The content of MDA was elevated whereas SOD was remarkably repressed in the miR-199a-5p mimic group. IL-6, IL-1β, and TNF-α were induced by miR-199a-5p overexpression while IL-10 was reduced by miR-199a-5p. Subsequently, surfactant protein D (SP-D) was predicted as the target of miR-199a-5p. The activation of NF-κB has been identified in sepsis. Herein, we demonstrated that inhibitor of miR-199a-5p contributed to IEC injury via targeting SP-D and inactivating the NF-κB pathway. These revealed miR-199a-5p exacerbated the intestinal barrier dysfunction via inhibiting SP-D and activating the NF-κB pathway in sepsis.

Highlights

Sepsis can be resulted from the infection and a systemic inflammation response [1]
These suggested that intestinal mucosal permeability and intestinal barrier function were dysregulated in mice models of sepsis
In our investigation, we observed that miR-199a-5p was remarkably increased in mice models of sepsis and isolated epithelial cells (IECs)

Summary

Introduction

Sepsis includes the dysfunction of an organ and systemic inflammatory response syndrome [1]. According to many published studies, intestinal barrier dysfunction contributes to the multiple organ dysfunction and the secondary bacterial translocation in sepsis [3]. Patients with sepsis often have intestinal barrier injury, and it is correlated with the severity of disease, which can affect the patient outcome. Several studies report that microRNA is closely associated with the progression of sepsis [9, 10]. MicroRNA dysregulation is correlated with sepsis, and they act as a crucial therapeutic target [11]. MiR155 can attenuate sepsis-triggered cardiac dysfunction via targeting JNK [12]. MiR-205-5b contributed to LPStriggered sepsis via inhibiting HMGB1 [14] MiR155 can attenuate sepsis-triggered cardiac dysfunction via targeting JNK [12]. miR-135a is increased and it can promote the myocardial inhibition in sepsis through modulating p38 MAPK/NF-κB [13]. miR-205-5b contributed to LPStriggered sepsis via inhibiting HMGB1 [14]

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