MiR-874-5p targets VDR/NLRP3 to reduce intestinal pyroptosis and improve intestinal barrier damage in sepsis

Abstract

Background: Vitamin D receptor (VDR) is associated with intestinal barrier damage in sepsis. However, the mechanism of action of miR-874-5p/VDR/NLRP3 axis in disease has not been clearly explained. Therefore, the main content of this study is to explore the mechanism of this axis in intestinal barrier damage in sepsis.

Methods: In order to confirm the progress of miR-874-5p regulation of VDR/NLRP3 pathway and its involvement in intestinal barrier damage in sepsis, a series of molecular biology and cell biology methods were carried out in this study. These include the establishment of cecal ligation puncture model, Western blot, RT-qPCR, hematoxylin and eosin staining, double luciferase reporting method, Fluorescence in situ hybridization, immunohistochemistry, and enzyme-linked immunosorption assay.

Results: The expression level of miR-874-5p was higher and that of VDR was lower in sepsis. miR-874-5p was negatively correlated with VDR. Inhibition of miR-874-5p expression increased the expression of VDR, decreased the expression of NLRP3, reduced caspase-1 activation and IL-1β secretion, reduced pyroptosis and inflammatory response, and thus protected the intestinal barrier damage in sepsis, all of which were reversed by the downregulation of VDR.

Conclusions: This study suggested that down-regulation of miR-874-5p or up-regulation of VDR could reduce intestinal barrier damage in sepsis, which may provide potential biomarkers and therapeutic targets for intestinal barrier damage in sepsis.

Keywords: Cecal ligation and puncture; Intestinal barrier dysfunction; Pyroptosis; Vitamin D receptor; miR-874-5p.