Abstract
BackgroundIntestinal barrier dysfunction is a significant clinical problem, commonly developing in a variety of acute or chronic pathological conditions. Herein, we evaluate the effect of microRNA-31 (miR-31) on intestinal barrier dysfunction through NF-κB/HIF-1α pathway by targeting HMOX1 in rats with sepsis.MethodsMale Sprague-Dawley rats were collected and divided into the sham group, and the cecum ligation and perforation group which was subdivided after CACO-2 cell transfection of different mimic, inhibitor, or siRNA. Levels of serum D-lactic acid, diamine oxidase and fluorescence isothiocyanate dextran, FITC-DX concentration, and bacterial translocation were detected. Superoxidedismutase (SOD) activity and malondialdehyde (MDA) content were evaluated using the colorimetric method and an automatic microplate reader, respectively. Additionally, the levels of tumor necrosis factor, interleukin (IL)-6, and IL-10 were tested using enzyme-linked immunosorbent assay. The expression of miR-31, HMOX1, NF-κB, HIF-1α, IκB, ZO-1 and Occludin were assessed by reverse transcription quantitative polymerase chain reaction and Western blot analysis.ResultsInhibition of miR-31 decreased intestinal mucosal permeability and intestinal barrier function. The increased levels of miR-31 could cause oxidative damage and affect the expression of inflammatory factors in intestinal tissue of rats. HMOX1 was confirmed as a target gene of miR-31. MiR-31 affected intestinal mucosal permeability and intestinal barrier function, as well as oxidative damage and inflammation level by regulating HMOX1. Down-regulation of miR-31 inhibited NF-κB/HIF-1α pathway related genes by regulating HMOX1 expression. Furthermore, inhibition of miR-31 increased survival rates of rats.ConclusionOverall, the current study found that inhibition of miR-31 protects against intestinal barrier dysfunction through suppression of the NF-κB/HIF-1α pathway by targeting HMOX1 in rats with sepsis.
Highlights
Intestinal barrier dysfunction is a significant clinical problem, commonly developing in a variety of acute or chronic pathological conditions
Thereby, the current study aims to investigate the effect of miR-31 on intestinal barrier dysfunction through the NF-κB/hypoxia-inducible factor (HIF)-1α pathway by targeting HMOX1 in sepsis
Results miR-31 affects intestinal mucosal permeability and intestinal barrier function Rats were subjected to CPL and administration of during sepsis in order to detect the role of miR-31 in intestinal mucosal permeability
Summary
Intestinal barrier dysfunction is a significant clinical problem, commonly developing in a variety of acute or chronic pathological conditions. The common clinical manifestations of sepsis are correlated with systemic inflammatory response syndrome and organ dysfunction, including hemodynamic instability, hypoxemia, and intestinal barrier dysfunction (Melvan et al 2010). Intestinal barrier dysfunction can result in secondary bacterial translocation and various clinical syndromes of multiple organ dysfunctions in sepsis (Fredenburgh et al 2011). Previous studies have demonstrated that anti-inflammatory genes targeting intestinal barrier dysfunction and relevant pathogenic factors can decrease bacterial translocation and unfavourable inflammatory responses, which thereby can increase survival rate in sepsis (Jiang et al 2013). MicroRNA (miRNA) dysregulation was reported to be correlated with clinical manifestations and inflammation, which thereby could serve as a potential therapeutic target against sepsis (Zhou et al 2015)
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