Selenium deficiency modulates necroptosis-mediated intestinal inflammation in broiler through the lncRNAWSF27/miRNA1696/GPX3 axis

Abstract Deficiency of selenium (Se), an important trace element, causes diarrhea and even death in broilers, thereby affecting the economic development of poultry production. Adding Se is one way to relieve this situation; however, it has not fundamentally resolved intestinal inflammation. Therefore, we sought a new strategy to alleviate intestinal inflammation by studying the specific mechanisms of Se deficiency. By replicating the Se-deficient broiler model and establishing a chicken small intestinal epithelial cell (CSIEC) model, we determined that Se deficiency caused intestinal oxidative stress and necroptotic intestinal inflammation in broilers by decreasing glutathione peroxidase (GPX) 3 expression. Simultaneously, the expression of long non-coding RNA (lncRNA)WSF27 decreased and that of miR-1696 increased in Se-deficient intestines. Recently discovered competing endogenous RNAs (ceRNAs) form novel regulatory networks, which were found that selenoproteins involved in ceRNA regulation. However, the mechanism of action of the non-coding RNA/GPX3 axis in Se-deficient broiler intestinal inflammation remains unclear. This study aimed to explore the mechanism through which Se deficiency regulates intestinal inflammation in broilers through the lncRNAWSF27/miR-1696/GPX3 axis. Our previous studies showed that lncRNAWSF27, miR-1696, and GPX3 have ceRNA-regulatory relationships. To further determine the role of the lncRNAWSF27/miR-1696/GPX3 axis in Se-deficient broiler intestinal inflammation, CSIEC models with GPX3 knockdown/overexpression, lncRNAWSF27 knockdown, or miR-1696 knockdown/overexpression were established to simulate intestinal injury. GPX3 knockdown, as well as lncRNAWSF27 and miR-1696 overexpression, aggravated cell damage. On the contrary, it can alleviate this situation. Our results reveal that mechanism of lncRNAWSF27/miR-1696/GPX3 regulated Se-deficient broiler intestinal inflammation. This conclusion enriches our understanding of the mechanism of intestinal injury caused by Se deficiency, and contributes to the diagnosis of Se-deficient intestinal inflammation and relevant drug development.