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miR-182-5p contributes to intestinal injury in a murine model of Staphylococcus aureus pneumonia-induced sepsis via targeting surfactant protein D.

Abstract：

:Sepsis is a severe clinical disease, which is resulted from the excessive host inflammation response to the infection. Growing evidence indicates that Staphylococcus aureus pneumonia is a significant cause of sepsis, which can lead to intestinal injury, inflammation, and apoptosis. Studies have shown that miR-182-5p can serve as a tumor oncogene or a tumor suppressive microRNA in various cancers, however, its biological role in sepsis is still uninvestigated. Here, we reported that miR-182-5p was obviously increased in S. aureus pneumonia mice models. Loss of miR-182-5p inhibited intestinal damage and intestinal apoptosis as indicated by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In addition, we observed the lack of miR-182-5p altered the local inflammatory response to pneumonia in the intestine. Elevated tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were observed in intestinal tissue of pneumonia groups compared with the shams. Furthermore, miR-182-5p knockout (KO) pneumonia group demonstrated decreased levels of intestinal TNF-α and IL-6. Primary murine intestinal epithelial cells were isolated and cultured in our investigation. We exhibited downregulation of miR-182-5p repressed intestinal epithelial cells apoptosis and rescued the cell viability. Meanwhile, miR-182-5p caused elevated cell apoptosis and reduced cell proliferation. Moreover, the surfactant protein D (SP-D) binds with the bacterial pathogens and remove the pathogens and apoptotic bodies, which exhibits important roles in modulating immune responses. It was displayed in our study that SP-D was greatly decreased in pneumonia mice models. SP-D was predicted as a downstream target of miR-182-5p. These data concluded that miR-182-5p promoted intestinal injury in S. aureus pneumonia-induced sepsis via targeting SP-D.

journal_name

J Cell Physiol

journal_title

Journal of cellular physiology

authors

Du X,Wei J,Tian D,Wu M,Yan C,Hu P,Wu X,Yang W,Yin T

doi

10.1002/jcp.28995

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

563-572

issue

eissn

0021-9541

issn

1097-4652

journal_volume

235

pub_type

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miR-182-5p contributes to intestinal injury in a murine model of Staphylococcus aureus pneumonia-induced sepsis via targeting surfactant protein D.