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. K E Y W O R D S miR-182, pneumonia, sepsis, surfactant protein D

The Cross-Talk Between Gut Microbiota and Lungs in Common Lung Diseases

“…Moreover, SP-D was reduced significantly in pneumonia mice models. It binds with the bacterial pathogens and eradicate the pathogens and apoptotic bodies, playing vital role in the regulation of immune responses (Du et al, 2019). In another study, it was demonstrated that SP-A and SP-D diminished severity of S. aureus pneumonia and gut mucosal injury.…”

“…The mechanisms by which the gut microbiota influences on the immune responses and inflammation in the lungs, and vice versa, are being extensively studied. The involvement of regulatory T cell subsets (Ohnmacht, 2016;Lee and Kim, 2017;Luu et al, 2017) and Toll-like receptors (TLRs) (O'Dwyer et al, 2016;Wang et al, 2018), inflammation cytokines and mediators (Scales et al, 2016), surfactant protein D (Du et al, 2019) and several other factors have been proposed as the underlying mechanisms, but many details unknown. Nevertheless, novel therapeutic strategies that target manipulation of gut microbiome by anti-biotics, probiotics, prebiotics, natural products, or diets have been attempted in various lung diseases by clinical and laboratory studies.…”

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

“…SP-D can repress the pneumonia severity and the intestinal injury of sepsis in rats [30]. Previously, we reported that miR-182-5p induces intestinal injury in a murine model of sepsis via targeting SP-D [31]. Currently, we found that SP-D was decreased in sepsis mice.…”

LncRNA CHRF aggravates myocardial ischemia/reperfusion injury by enhancing autophagy via modulation of the miR‐182‐5p/ATG7 pathway

“…[ 38 ] miR‐182‐5p targets surfactant protein D to facilitate intestinal injury in sepsis induced by Staphylococcus aureus pneumonia. [ 39 ] miR‐182‐5p regulates Cofilin 1 to affect cell proliferation, migration, and invasion in human bladder cancer. [ 40 ] However, the relationship between CHRF and miR‐182‐5p in myocardial I/R injury is not clear.…”